Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE.Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.Teprotide: A synthetic nonapeptide (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) which is identical to the peptide from the venom of the snake, Bothrops jararaca. It inhibits kininase II and ANGIOTENSIN I and has been proposed as an antihypertensive agent.Enalaprilat: The active metabolite of ENALAPRIL and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat.Peptidyl-Dipeptidase A: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 188.8.131.52.Cilazapril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat.Perindopril: An angiotensin-converting enzyme inhibitor. It is used in patients with hypertension and heart failure.Renin: A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 184.108.40.206.Tetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.Lisinopril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Angiotensin I: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.Renin-Angiotensin System: A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.ThiazepinesAngiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.Renal Circulation: The circulation of the BLOOD through the vessels of the KIDNEY.Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.Dilleniaceae: A plant family of the order Dilleniales, subclass Dilleniidae, class Magnoliopsida.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Rats, Inbred SHR: A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.TetrazolesAntihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Capillary Resistance: The vascular resistance to the flow of BLOOD through the CAPILLARIES portions of the peripheral vascular bed.Kinetics: The rate dynamics in chemical or physical systems.Folic Acid Antagonists: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)Diet, Sodium-Restricted: A diet which contains very little sodium chloride. It is prescribed by some for hypertension and for edematous states. (Dorland, 27th ed)Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.3-Mercaptopropionic Acid: An inhibitor of glutamate decarboxylase. It decreases the GAMMA-AMINOBUTYRIC ACID concentration in the brain, thereby causing convulsions.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Receptor, Angiotensin, Type 2: An angiotensin receptor subtype that is expressed at high levels in fetal tissues. Many effects of the angiotensin type 2 receptor such as VASODILATION and sodium loss are the opposite of that of the ANGIOTENSIN TYPE 1 RECEPTOR.Hypertension, Renovascular: Hypertension due to RENAL ARTERY OBSTRUCTION or compression.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Aldosterone: A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.Oligopeptides: Peptides composed of between two and twelve amino acids.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Dipeptides: Peptides composed of two amino acid units.Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Angiotensins: Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Imidazolidines: Compounds based on reduced IMIDAZOLINES which contain no double bonds in the ring.Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Lysine Carboxypeptidase: A metallocarboxypeptidase that removes C-terminal basic amino acid from peptides and proteins, with preference shown for lysine over arginine. It is a plasma zinc enzyme that inactivates bradykinin and anaphylatoxins.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.Biphenyl CompoundsImidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.Organ Size: The measurement of an organ in volume, mass, or heaviness.Benzazepines: Compounds with BENZENE fused to AZEPINES.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Kinins: A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588)Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.Hypertrophy, Left Ventricular: Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Natriuresis: Sodium excretion by URINATION.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Rats, Inbred WKY: A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR).Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Compliance: Distensibility measure of a chamber such as the lungs (LUNG COMPLIANCE) or bladder. Compliance is expressed as a change in volume per unit change in pressure.Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 220.127.116.11.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Kidney Cortex: The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Heart: The hollow, muscular organ that maintains the circulation of the blood.Renal Artery Obstruction: Narrowing or occlusion of the RENAL ARTERY or arteries. It is due usually to ATHEROSCLEROSIS; FIBROMUSCULAR DYSPLASIA; THROMBOSIS; EMBOLISM, or external pressure. The reduced renal perfusion can lead to renovascular hypertension (HYPERTENSION, RENOVASCULAR).Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Albuminuria: The presence of albumin in the urine, an indicator of KIDNEY DISEASES.Fibrinolysis: The natural enzymatic dissolution of FIBRIN.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Zanamivir: A guanido-neuraminic acid that is used to inhibit NEURAMINIDASE.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Angiotensin II Type 1 Receptor Blockers: Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.Technetium Tc 99m Pentetate: A technetium imaging agent used in renal scintigraphy, computed tomography, lung ventilation imaging, gastrointestinal scintigraphy, and many other procedures which employ radionuclide imaging agents.Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Vasomotor System: The neural systems which act on VASCULAR SMOOTH MUSCLE to control blood vessel diameter. The major neural control is through the sympathetic nervous system.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Kidney Function Tests: Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.Cardiac Output, Low: A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Forearm: Part of the arm in humans and primates extending from the ELBOW to the WRIST.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Enzymes: Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.PyridazinesDiuresis: An increase in the excretion of URINE. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Hypertension, Renal: Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN.Propionates: Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Aorta: The main trunk of the systemic arteries.Tetrahydrofolate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 18.104.22.168.Arginine: An essential amino acid that is physiologically active in the L-form.Single-Blind Method: A method in which either the observer(s) or the subject(s) is kept ignorant of the group to which the subjects are assigned.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cytochrome P-450 CYP2D6: A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Guanidines: A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Angiotensinogen: An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver and secreted into blood circulation. Angiotensinogen is the inactive precursor of natural angiotensins. Upon successive enzyme cleavages, angiotensinogen yields angiotensin I, II, and III with amino acids numbered at 10, 8, and 7, respectively.Endothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 22.214.171.124.Atenolol: A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Diabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.Recombinant Proteins: Proteins prepared by recombinant DNA technology.CreatinineNitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Plasminogen Activator Inhibitor 1: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.Coronary Circulation: The circulation of blood through the CORONARY VESSELS of the HEART.Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Sulfonamides: A group of compounds that contain the structure SO2NH2.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Diastole: Post-systolic relaxation of the HEART, especially the HEART VENTRICLES.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Stroke Volume: The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Myocardial Contraction: Contractile activity of the MYOCARDIUM.Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery.Kidney Failure, Chronic: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Cardiac Pacing, Artificial: Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Exercise Test: Controlled physical activity which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).
Cytochrome P-450 enzyme induction and inhibition Potent inducers. Potent inhibitors. Substrates ... Drugs that modify cytochrome P-450 enzyme are referred to as either inhibitors or inducers. Enzyme inhibitors block the ... 2. Change in enzyme activity:. Many substances can influence the P-450 enzyme mechanism. Drugs interact with the enzyme family ... "Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor". J. Pharmacol. Exp. Ther. ...
Synthetic inhibitors of the enzyme have been discovered. However, no AANAT inhibitor with potent in vivo activity has been ... Khalil EM, De Angelis J, Ishii M, Cole PA (October 1999). "Mechanism-based inhibition of the melatonin rhythm enzyme: ... Khalil, Ehab M.; Philip A. Cole (6 June 1998). "A Potent Inhibitor of the Melatonin Rhythm Enzyme". J. Am. Chem. Soc. 120 (24 ... Khalil EM, Cole PA (1998). "A potent inhibitor of the melatonin rhythm enzyme". J. Am. Chem. Soc. 120 (24): 6195-6196. doi: ...
Kim YJ, Uyama H (Aug 2005). "Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and ... Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly ... Journal of Enzyme Inhibition and Medicinal Chemistry. 17 (4): 207-18. doi:10.1080/14756360210000010923. PMID 12530473. Sollai, ... The enzymes found in plant, animal, and fungal tissue frequently differ with respect to their primary structure, size, ...
... a new selective serine carboxypeptidase inhibitor from Streptomyces lavendofoliae MJ908-WF13". Journal of enzyme inhibition. 11 ... a new selective serine carboxypeptidase inhibitor from Streptomyces lavendofoliae MJ908-WF13". Journal of enzyme inhibition. 11 ...
"The evaluation of novel natural products as inhibitors of human glutathione transferase P1-1". Journal of Enzyme Inhibition and ... Douglas KT (1987). "Mechanism of action of glutathione-dependent enzymes". Advances in Enzymology and Related Areas of ... The porcine pi-class enzyme pGTSP1-1 was the first GST to have its structure determined, and it is representative of other ... The activity of GSTs is dependent upon a steady supply of GSH from the synthetic enzymes gamma-glutamylcysteine synthetase and ...
It enhances other protease inhibitors through the inhibition of CYP3A4, a liver enzyme. While ritonavir is a protease inhibitor ... The enzyme CYP3A4, a member of the Cytochrome P450 enzyme family, is present mostly in the liver but also in the lining of the ... Such enzymes present in the GI tract are a first line defense against toxic substances; this allows the body to metabolize away ... Works analogous to HU and RV only the enzyme inhibited is IMPDH which leads to depletion of the dNTP named dGTP which causes ...
Angiotensin inhibition by either an angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist may reduce ... One meta analysis found a protective effect from an angiotensin converting enzyme polymorphisms on migraine. Migraines may be ... "Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis". The ...
However, some do not act via inhibition of this enzyme, and instead act via other, poorly elucidated mechanisms. Unlike ... Many disulfiram-like drugs act as inhibitors of acetaldehyde dehydrogenase similarly to disulfiram. ... They are caused by accumulation of acetaldehyde, a major but toxic metabolite of alcohol formed by the enzyme alcohol ... acetaldehyde dehydrogenase inhibitors and other disulfiram-like drugs, alcohol dehydrogenase inhibitors such as fomepizole ( ...
... the profenofos mechanism of action is via the inhibition of the acetylcholinesterase enzyme. Although it is used in the form of ... underlie differences in their behavior as acetylcholinesterase enzyme inhibitors compared to the rest of the OP class. In one ... a racemate, the S(-) isomer is a more potent inhibitor. Profenofos can be synthesized by reacting phosphorus oxychloride with ...
Inhibition of the Enzyme by Hydroxyurea, Hydroxylamine, and Acetohydroxamic Acid". J Biol Chem. 240: 2407-2414. PMID 14304845. ... salicylhdroxamic acid acts as an inhibitor of the enzyme, blocking the largely uninhibited flow of electrons through AOX. AOX ... The molecule is similar to urea but is not hydrolyzable by the urease enzyme. It is also a trypanocidal agent. When ... Salicylhydroxamic acid (SHA or SHAM) is a drug that is a potent and irreversible inhibitor of bacterial and plant urease ...
Gossypol's main function in the cotton plant is to act as an enzyme inhibitor. An example of gossypol's enzyme inhibition is ... Secondary metabolism is connected to primary metabolism by using building blocks and biosynthetic enzymes derived from primary ... it triggers specific enzymes that fight carcinogens. Good dietary sources of Flavonoids are all citrus fruits, which contain ... while reducing phytic acid and protease inhibitors, ultimately increasing the nutritional value. Cooking can also reduce the ...
The excess dopamine resulting from inhibition of the dopamine β-hydroxylase enzyme increases unpleasant symptoms such as ... Dopamine reuptake inhibitors (DRIs) or dopamine transporter (DAT) inhibitors such as methylphenidate (Ritalin), bupropion ( ... Dopamine β-hydroxylase inhibitors like disulfiram (Antabuse), which can be used in the treatment of addiction to cocaine and ... Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA ...
In competitive inhibition, the inhibitor binds to the active site, thus preventing enzyme-substrate interaction. In non- ... competitive inhibition, the inhibitor binds to an allosteric site, which alters the active site and makes it inaccessible to ... Protease inhibitors are usually proteins with domains that enter or block a protease active site to prevent substrate access. ... Cysteine proteases, also known as thiol proteases, are enzymes that degrade proteins. These proteases share a common catalytic ...
IVF controls proteolytic inhibition through interactions with active site of enzyme. Picornavirus 3C protease's infectivity and ... So far, 3C protease inhibitors have been discovered and used to monitor effects of picornavirus. Lots of testing is going into ... Currently no anti-picornal drug targeting 3C protease is in the market yet, but inhibitors such as rupintrivir and pyrazoles ... Picornain 3C (EC 126.96.36.199, Picornain 3C is a protease and endopeptidase enzyme found in the picornavirus, that cleaves peptide ...
Ambenonium (as ambenonium dichloride, trade name Mytelase) is a cholinesterase inhibitor used in the management of myasthenia ... Ambenonium exerts its actions against myasthenia gravis by competitive reversible inhibition of acetylcholinesterase, the ... enzyme responsible for the hydrolysis of acetylcholine. Myasthenia gravis occurs when the body produces antibodies against ... Hodge AS, Humphrey DR, Rosenberry TL (May 1992). "Ambenonium is a rapidly reversible noncovalent inhibitor of ...
It was developed in the 1980s as a new antiinflammatory and prostaglandin synthesis inhibitor, acting through inhibition of the ... enzyme cyclooxygenase (COX). However, pravadoline was found to exhibit unexpectedly strong analgesic effects, which appeared at ... ten times smaller than the effective anti-inflammatory dose and so could not be explained by its action as a COX inhibitor. ...
It has been shown to act as an acetylcholinesterase inhibitor, and inhibits biosynthesis of dopamine via inhibition of the ... enzyme tyrosine hydroxylase. According to the Dorlands Medical Dictionary, it "inhibits the reflex and motor activities of ... Zhang, Y. H.; Shin, J. S.; Lee, S. S.; Kim, S. H.; Lee, M. K. (Aug 1997). "Inhibition of Tyrosine Hydroxylase by Bulbocapnine ...
Inhibition of enzymes involved in purine biosynthesis has been exploited as a potential drug target for chemotherapy. Cancer ... of folate based inhibitors have been found to be particularly challenging as the inhibitors also down regulate the enzyme ... as it is kinetically and chemically competent to carry out the formylation reaction in the enzyme. A enzyme phosphate ... The enzyme is a member of the ATP-grasp superfamily of proteins. A sequential mechanism has been proposed for PurT GAR ...
Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Research communications in ... Mellors A, Tappel A, (July 1966). "Quinones and Quinols as Inhibitors of Lipid Peroxidation". Lipids 1 (4): 282-284. PMID ... Coenzym Q10 blev opdaget i 1957 af professor Frederick L. Crane og hans kolleger ved University of Wisconsin-Madison* Enzyme ... 1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clinical cancer research ...
Inhibitor (RI). *Releaser (RA). *♦ Miscellaneous: Precursor. *Cofactor. Classes. Enzyme. see Enzyme inhibition ... Examples of reuptake modulators include reuptake inhibitors (transporter blockers) and reuptake enhancers. ...
Enzymes can be targeted with enzyme inhibitors. Receptors are typically categorised based on structure and function. Major ... Enzyme. see Enzyme inhibition. Ion channel. See Ion channel modulators. Receptor &. transporter. ... James Smith; Viktor Stein (2009). "SPORCalc: A development of a database analysis that provides putative metabolic enzyme ... Molecular targets in pharmacology include receptors, enzymes and membrane transport proteins. ...
Inhibitor (RI). *Releaser (RA). *♦ Miscellaneous: Precursor. *Cofactor. Classes. Enzyme. see Enzyme inhibition ... Reversible Acetylcholinesterase inhibitor agents such as physostigmine can be used as an antidote in life-threatening cases. ...
Monoamine oxidase inhibitors allow reuptake of biogenic amine neurotransmitters from the synapse, but inhibit an enzyme which ... Enzyme. see Enzyme inhibition. Ion channel. See Ion channel modulators. Receptor &. transporter. ... Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are widely used antidepressants that specifically block the ... "Depression Medication: Antidepressants, SSRIs, Antidepressants, SNRIs, Antidepressants, TCAs, Antidepressants, MAO Inhibitors, ...
"In-vitro and in-vivo Inhibition of Rat Neutral Endopeptidase and Angiotensin Converting Enzyme with the Vasopeptidase Inhibitor ... It acts as a vasopeptidase inhibitor. It inhibits both angiotensin-converting enzyme (ACE) and neutral endopeptidase ( ...
"Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP ... APPBP1 also bonds with UBA3 (ubiquitin-like protein-activating enzyme 3) to form the NEDD8 activating enzyme (NAE). Activated ... a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a ... "A phase I study of the investigational NEDD8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924) in patients with ...
Cucurbitaceae) induced inhibition of D-glucose, L-tyrosine and fluid transport across rat everted intestinal sacs in vitro». ... Biodiversity As A Source of Selective Inhibitors of CHIKV Replication». Antiviral Research. doi:10.1016/j.antiviral.2011.03.048 ... Traditional Medicinal Herbs and Food Plants Have the Potential to Inhibit Key Carbohydrate Hydrolyzing Enzymes In Vitro and ...
In uncompetitive inhibition, the inhibitor binds only to the substrate-enzyme complex. This type of inhibition causes Vmax to ... In mixed inhibition, the inhibitor can bind to the enzyme at the same time as the enzymes substrate. However, the binding of ... Uncompetitive inhibition occurs when the inhibitor binds only to the enzyme-substrate complex, not to the free enzyme; the EIS ... Reversible inhibitors. Types of reversible inhibitors. Reversible inhibitors attach to enzymes with non-covalent ...
Competitive CYP2C9 Inhibitors: Enzyme Inhibition Studies, Protein Homology Modeling, and Three-Dimensional Quantitative ... Competitive CYP2C9 Inhibitors: Enzyme Inhibition Studies, Protein Homology Modeling, and Three-Dimensional Quantitative ... Competitive CYP2C9 Inhibitors: Enzyme Inhibition Studies, Protein Homology Modeling, and Three-Dimensional Quantitative ... Competitive CYP2C9 Inhibitors: Enzyme Inhibition Studies, Protein Homology Modeling, and Three-Dimensional Quantitative ...
Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition ... Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition ... Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition ... Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition ...
Tag: Entinostat reversible enzyme inhibition. Aim: In todays study, a new formulation of HBsAg vaccine was. Posted on June 29 ... After 3 x immunization, this vaccine network marketing leads to a humoral immune system Entinostat reversible enzyme inhibition ... In Entinostat reversible enzyme inhibition this paper, we hypothesized that formulating HBsAg in Montanide ISA 266 as a water- ... a more potent humoral immunity via interaction with Tfh cells in the germinal center Entinostat reversible enzyme inhibition to ...
... data obtained with antisera raised against LORF and leech ACE showed a colocalization between the enzyme and its inhibitor in ... Fifty-four percent of insect ACE activity is inhibited with 50 micro m IPEP and 35% inhibition with LORF (25 mm). Extending the ... the concentration of inhibitor. We demonstrated that LORF (IPEPYVWD), a neuropeptide previously found in leech brain, is able ... and its inhibition by a novel natural antagonist, the leech osmoregulator factor (LORF) using capillary zonal electrophoresis ...
BBC2RepSox reversible enzyme inhibition Background In represents the weights for input edges from node to. May 7, 2019. Sherri ... RepSox reversible enzyme inhibition Supplementary Materialspolymers-10-00839-s001. examined. We found that the presence of HGC ... Next, some adjustments in OCR was assessed when cells had been consecutively treated with RepSox reversible enzyme inhibition 1 ... When cells RepSox reversible enzyme inhibition reached ~70% confluence, the tradition medium was changed with XF Assay moderate ...
ARRY-438162 enzyme inhibitor The rats had been fed with a standard diet with drinking water prior to the treatment and ... Posted under Miscellaneous Opioids Tags: ARRY-438162 enzyme inhibitor, Rabbit Polyclonal to STEA2 ... Peritonitis was not observed in rats ARRY-438162 enzyme inhibitor after anesthesia. After anesthesia, the trachea was exposed ... Inhibition of c-Met for tumor therapy. Data Availability StatementThe analyzed data models generated during the present study ...
Enzyme Inhibition Assay. The assay was performed, and samples were analyzed as described before (Niegowski et al., 2014a). ... Inhibition of Human Recombinant LTC4S. We found that TK04, TK04a, and TK05 are nanomolar inhibitors of the isolated human ... Inhibition of LTC4S in Differentiated MM6 Cells. To study the cellular activity of the inhibitors, we chose differentiated MM6 ... The binding site of the compounds in this docking study supports the competitive mode of inhibition for all three inhibitors ...
745-65-3 A 803467 AG-490 BMP2 Bmp3 BYL719 CAB39L CB-7598 CD33 CI-1011 CXADR Dalcetrapib DAMPA EMR1 Enzastaurin enzyme inhibitor ... Posted in General Tagged AZD8055 reversible enzyme inhibition, Istradefylline supplier, Rabbit Polyclonal to EFNA3, RHOA ... Tag Archives: AZD8055 reversible enzyme inhibition. Supplementary MaterialsS1 Desk: Anonymized individual data. survival and ... The proliferation index detected by Ki-67 was found to end AZD8055 reversible enzyme inhibition up being 20%. The immunostains ...
transcription, translation, enzyme activity, and intracellular signaling) BMN673 reversible enzyme inhibition and mobile ... 1representative hematoxylin BMN673 reversible enzyme inhibition and eosin-stained mammary gland sections illustrating ... One proteins that is crucial for Zn2+ administration in BMN673 reversible enzyme inhibition the mammary gland may be the ... to hypothesize that cytoplasmic Zn2+ deposition in ZnT2-attenuated MECs may be the aspect BMN673 reversible enzyme inhibition ...
ABL AG-1024 AMG 548 ARRY334543 ATN1 BI-1356 reversible enzyme inhibition BIBX 1382 BMS-777607 BMS-790052 BTZ038 CXCL5 ETV7 ... Bortezomib reversible enzyme inhibition The developing originally incorporates a large number of nuclei from both original ... The limited details from both of these types illustrates how small is Bortezomib reversible enzyme inhibition well known about ... This frequency is usually one piece of evidence Bortezomib reversible enzyme inhibition for meiosis during zygospore ...
... degrading enzymes in pterygium fibroblasts contributed to the Cidofovir reversible enzyme inhibition development and ... Tag Archives: Cidofovir reversible enzyme inhibition Background The pterygium is a rise onto the cornea of fibrovascular. ... Posted in Blog , Tagged Cidofovir reversible enzyme inhibition, Mouse monoclonal to PRDM1 ... Mouse monoclonal to PRDM1 The pterygium mind Cidofovir reversible enzyme inhibition and body had been confirmed, and excised ...
Cancer immunotherapy; Enzyme inhibition; High throughput screening; In silico drug design; Indoleamine 2,3-dioxygenase; ... One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead ... Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.. ... Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library ...
IMD 0354 reversible enzyme inhibition Supplementary Materials Desk S1. organs, avoiding unwanted loss of adherent cells ... This entry was posted in Blogging and tagged ANGPT1, CTLA1, GM 6001 ic50, IMD 0354 reversible enzyme inhibition. ... IMD 0354 reversible enzyme inhibition 2001; Berridge et al., 2003; Szabadkai and Rizzuto, 2004; Yi et al., 2004; Brough et al ... IMD 0354 reversible enzyme inhibition Frey et al., 2002). The molecular determinants of the crosstalk, however, remain largely ...
multidrug resistance by tyrosine kinase inhibitors in cell biology. Menu. Skip to content *Home ... Chemical inhibition of ceramide biosynthesis impairs utilization of nutrient reserves AZD6738 reversible enzyme inhibition in ... This entry was posted in LTD4 Receptors and tagged AZD6738 reversible enzyme inhibition, RASGRP2 on December 23, 2019. by ... Tag Archives: AZD6738 reversible enzyme inhibition. Supplementary MaterialsTABLE?S1. FIG?S1. Data visualization analysis. (a ...
In the present work, a chemical library of 250 compounds was evaluated to determine their inhibition capability on the protein ... The data reported here support these compounds as hits for the design more potent and selective inhibitors against PTP1B in the ... Docking and molecular dynamics studies revealed that the three inhibitors made interactions with residues at the secondary ... Keywords: protein tyrosine phosphatase 1B; type 2 diabetes; benzimidazole derivatives; enzyme inhibition; docking; molecular ...
Histone deacetylase (HDAC) Inhibitors Database. Recent Posts. * Supplementary MaterialsSupplementary Information 41467_2017_174 ... Posted in Ca2+ ChannelsH 89 dihydrochloride reversible enzyme inhibition, Rabbit Polyclonal to Claudin 5 (phospho-Tyr217). ... Tag: H 89 dihydrochloride reversible enzyme inhibition. sporozoites invade host hepatocytes and develop as liver stages (LS) ... Due to the high H 89 dihydrochloride reversible enzyme inhibition A/T nucleotide content of DNA, many malarial proteins contain ...
Purchase Monoamine Oxidases and their Inhibitors, Volume 100 - 1st Edition. Print Book & E-Book. ISBN 9780123864673, ... KINETIC BEHAVIOR AND REVERSIBLE INHIBITION OF MONOAMINE OXIDASES-ENZYMES THAT MANY WANT DEAD ... Monoamine Oxidases and their Inhibitors, Volume 100 1st Edition. 0 star rating Write a review ... In this volume, invited experts provide authoritative reviews on various aspects of Monoamine Oxidase and its Inhibitors. ...
ENZYME INHIBITION ASSAY. Inhibitor conc., mM. 0.001. 0.0025. 0.005. 0.01. 0.02. 0.3125. 0.625. 1.25. 5. 10. ... If one wished to carry out enzyme assays, where the enzyme is an expensive reagent, one could have the enzyme provided from the ... In the next study, the effect of enzyme inhibitor was investigated. The channel was 1 mm in width. Approximately 30 nl of ... Where the label is an enzyme, the liquid in the zone could include substrate for the enzyme, where the product of the substrate ...
Copyright 2020, Progress in the Preclinical Discovery and Clinical Development of PI3K inhibitors ... Bardoxolone methyl reversible enzyme inhibition, FGF23Read More →. Search for: Recent Posts. * Supplementary MaterialsS1 Table ... Bardoxolone methyl reversible enzyme inhibition, GSNRead More →. Glutamate (AMPA) Receptors. Data Availability StatementThe ... Bardoxolone methyl reversible enzyme inhibition. Glucagon and Related Receptors. Hypereosinophilia (HE) is identified as having ...
Kinetic analysis of enzyme inhibition and identification of ther reactive site ... a leech derived inhibitor of factor X a. ... Kinetic analysis of enzyme inhibition and identification of ... Antistasin, a leech derived inhibitor of factor X a. ...
Intereukin 1 (beta)-concerting enzyme (ICE) inhibition and serine proteases inhibitor prevented up-regulation of cyclin E and ... Intereukin 1 (beta)-concerting enzyme (ICE) inhibition and serine proteases inhibitor prevented up-regulation of cyclin E and ... Conference Paper: Intereukin 1 (beta)-concerting enzyme (ICE) inhibition and serine proteases inhibitor prevented up-regulation ...
Table 3: Percent enzyme inhibition shown by plant extracts with liver glucosidases. ...
Angiotensin-Converting Enzyme Inhibitors. Protease Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological ... Trial of Angiotensin Converting Enzyme Inhibition in Infants With Single Ventricle--Pediatric Heart Network (ISV). The safety ... Enalapril (angiotensin converting enzyme inhibitor). Drug: Enalapril Enalapril to target dose of .4mg/kg/day divided to twice ... Rationale and design of a trial of angiotensin-converting enzyme inhibition in infants with single ventricle. Am Heart J. 2009 ...
Angiotensin-Converting Enzyme Inhibitors. Protease Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological ... Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition. The safety and scientific validity of this study is ... Measure the renal blood oxigenation after angiotensin converting enzyme inhibition [ Time Frame: up to 12 months ]. ... Renal Oxygen Content is Increased in Healthy Subjects After Angiotensin Converting Enzyme Inhibition. ...
Current Enzyme InhibitionKineticsTreatment with angiotensin convertingKinase inhibitorSubstrateJournal of Enzyme InhibitionSmall moleculeToxicityMonoamine Oxidase InProteasesAntihypertensive AgentsRenin-Angiotensin SysteInhibitSelective inhibitionBiosynthesisDipeptidyl peptidase-HumansPharmacologyMechanismsReactionsHigh-throughput screenTherapeuticMetabolicCarbonicReceptorsClinicalInactivationConcentrationInteractionsTypes of inhibitionSerineRibonuclease inhibitorMedicinal ChemistryAssaySynthesisMetabolismDiureticsAngioedemaCellularLiverPurineCompounds demonstrate potentRenalSpecific inhibitionAngiotensin IIMorbidity and mortaTumor growthPotency
- He is Editor-in-Chief of Expert Opinion on Therapeutic Patents, Journal of Enzyme Inhibition and Medicinal Chemistry, Current Enzyme Inhibition, etc. (benthamscience.com)
- Current Enzyme Inhibition Journal was launched in 2005. (benthamscience.com)
- Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. (ingentaconnect.com)
- Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition. (ingentaconnect.com)
- enzyme kinetics , rate of reaction and 2 more. (protocol-online.org)
- Three types of inhibition (competitive, uncompetitive, noncompetitive/mixed) and reaction with no inhibitor are compared for an enzyme reaction that obeys Michaelis-Menten kinetics. (wolfram.com)
- Kinetics of Enzyme Action. (researchandmarkets.com)
- Kinetics of Enzyme Action explores, in depth, the characteristics and applications of these proteins and their vital role in the development of new medicines by placing the subject of enzymology in a historical context that enriches and heightens understanding of this complex science. (researchandmarkets.com)
- From discussion of the early developments in the kinetics of enzymatic reactions to fresh insights on contemporary enzymology, Kinetics of Enzyme Action offers comprehensive coverage of a discipline that holds vital significance for all pharmaceutical practitioners. (researchandmarkets.com)
- Conclusion: Treatment with dipeptidyl peptidase-4 inhibitors must be carefully considered and monitored especially during concurrent treatment with angiotensin converting enzyme-inhibitors or when treating patients with a known predisposition to angioedema. (eurekaselect.com)
- Angio-oedema in relation to treatment with angiotensin converting enzyme inhibitors. (springer.com)
- GSK690693 is a novel ATP-competitive, low-nanomolar pan-Akt kinase inhibitor. (aacrjournals.org)
- However, the number of structural classes that act as CDK inhibitors is limited, and most of them derive from relatively nonspecific protein kinase inhibitor scaffolds such as staurosporines ( 27 -29 ), flavonoids ( 29 ), indigoids ( 30 ), paulones ( 31 ), and purines ( 32 ). (aacrjournals.org)
- An enzyme binding site that would normally bind substrate can alternatively bind a competitive inhibitor , preventing substrate access. (wikipedia.org)
- Binding site in blue, inhibitor in green, and substrate in black. (wikipedia.org)
- The binding of an inhibitor can stop a substrate from entering the enzyme's active site and/or hinder the enzyme from catalyzing its reaction. (wikipedia.org)
- In contrast, reversible inhibitors bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme , the enzyme-substrate complex, or both. (wikipedia.org)
- They are classified according to the effect of varying the concentration of the enzyme's substrate on the inhibitor. (wikipedia.org)
- In competitive inhibition , the substrate and inhibitor cannot bind to the enzyme at the same time, as shown in the figure on the right. (wikipedia.org)
- the substrate and inhibitor compete for access to the enzyme's active site. (wikipedia.org)
- This type of inhibition can be overcome by sufficiently high concentrations of substrate ( V max remains constant), i.e., by out-competing the inhibitor. (wikipedia.org)
- Competitive inhibitors are often similar in structure to the real substrate (see examples below). (wikipedia.org)
- In uncompetitive inhibition , the inhibitor binds only to the substrate-enzyme complex. (wikipedia.org)
- In non-competitive inhibition , the binding of the inhibitor to the enzyme reduces its activity but does not affect the binding of substrate. (wikipedia.org)
- Dear all, I did the ITC (isothermal titration calorimetry) between an enzyme with its known substrate on Microcal ITC200. (protocol-online.org)
- while titrating substrate to enzyme seems to be the sum of heats from the two controls. (protocol-online.org)
- I did not expect that I cannot even observe the binding curve in titration between the enzyme and its substrate! (protocol-online.org)
- Borowski P, Heiland M, Feucht HH, Laufs R. (1999a) Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC: evidences for action on the level of substrate and enzyme. (edu.pl)
- 2002) Characterization of imidazo[4,5-d]pyridazine nucleosides as modulators of unwinding reaction mediated by West Nile virus nucleoside triphosphatase/helicase: evidence for activity on the level of substrate and/or enzyme. (edu.pl)
- 1. The principal methods used for the assessment of enzyme induction and enzyme inhibition are measurement of the pharmacokinetics of a model compound (probe drug), analysis of drug metabolism in vitro, and determination of changes in the disposition of, and endogenous substrate for, the enzyme of interest. (nih.gov)
- adding more substrate minimizes the inhibitor effect. (wolfram.com)
- adding more substrate does not overcome this type of inhibition since the inhibitor does not compete with the substrate for the enzyme sites. (wolfram.com)
- Enzymes with a low Km have a high affinity to their substrate, as opposed to enzymes with a high Km which have a low affinity for their substrate. (brainscape.com)
- It introduces readers to a wide range of topics invaluable for helping them discover and kinetically characterize enzyme inhibitors from simple, one-substrate enzyme reactions to the more complex two-substrate enzymes reactions. (researchandmarkets.com)
- Insulin indirectly relieves GS inhibition ( 4 , 5 ) through a signaling cascade beginning with phosphorylation of substrates, including insulin receptor substrate 1 (IRS-1), by the tyrosine kinase activity of activated insulin receptor ( 6 , 7 ). (diabetesjournals.org)
- In mixed inhibition, the inhibitor can bind to the enzyme at the same time as the enzyme's substrate. (wikipedia.org)
- However, the binding of the inhibitor affects the binding of the substrate, and vice versa. (wikipedia.org)
- This type of inhibition can be reduced, but not overcome by increasing concentrations of substrate. (wikipedia.org)
- Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2). (nature.com)
- Antibodies or small molecule inhibitors targeted to ErbB-2 or EGFR are either approved for therapy or are showing encouraging safety and efficacy profiles in clinical trials. (aacrjournals.org)
- Because of the critical role of the CDKs in the regulation of the cell cycle and the observed expression/activity pattern in most human cancers, considerable effort has been focused on the development of small molecule inhibitors ( 24 -26 ). (aacrjournals.org)
- A considerable number of thrombin inhibitors developed so far suffer from poor selectivity, inherent toxicity, high-plasma protein binding, poor metabolic stability, rapid elimination from the blood, low anticoagulant activity, or poor oral bioavailability, to name but a few problems. (pnas.org)
- As selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed, pediatricians, child psychiatrists, and emergency physicians should be familiar with the manifestations of serotonin syndrome resulting from pediatric SSRI toxicity. (medscape.com)
- The compound is a specific inhibitor of multiple HDAC isoforms that potently inhibits tumor growth in vivo with acceptable toxicity. (pnas.org)
- The risk of renal toxicity related to ACE-inhibitors was rather feared when these compounds were introduced as therapeutic agents for hypertension and chronic heart failure (CHF) 1-4 . (scielo.br)
- Angiotensin-converting enzyme inhibitors and lithium toxicity. (webmd.com)
- Although SSRIs are commonly linked to serotonin syndrome, many other drugs (eg, amphetamines, monoamine oxidase inhibitors [MAOIs], TCAs, lithium) have the potential of causing hyperserotonergic symptoms. (medscape.com)
- Knoll, J, Magyar K. Some puzzling pharmacological effects of monoamine oxidase inhibitors. (springer.com)
- This can help control enzymes that may be damaging to a cell, like proteases or nucleases . (wikipedia.org)
- Synthetic inhibitors of trypsin-like serine proteases were covalently immobilized to polymeric materials to passivate coagulation enzymes during blood contact. (duhnnae.com)
- In this problem, Dr. Fedeles explores the mechanisms of inhibition enzymes, in this case, proteases. (mit.edu)
- Hitoshi Yoshiji, Ryuichi Noguchi, Yasuhide Ikenaka, Mitsuteru Kitade, Kosuke Kaji, Tatsuhiro Tsujimoto, Masahito Uemura and Hiroshi Fukui, " Renin-Angiotensin System Inhibitors as Therapeutic Alternatives in the Treatment of Chronic Liver Diseases", Current Medicinal Chemistry (2007) 14: 2749. (eurekaselect.com)
- A medicinal enzyme inhibitor is often judged by its specificity (its lack of binding to other proteins) and its potency (its dissociation constant , which indicates the concentration needed to inhibit the enzyme). (wikipedia.org)
- Other cellular enzyme inhibitors are proteins that specifically bind to and inhibit an enzyme target. (wikipedia.org)
- The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. (dtu.dk)
- Injection of N-[N-(3,5-difluorophenylacetyl)-1-alanyl] phenylglycine t-butyl ester could inhibit the Notch pathway and such an inhibition protected lung tissue and reduced lung inflammation caused by mechanical ventilation. (healthyconnectionsinc.com)
- 2-HG is structurally similar to α-KG and has been shown to inhibit α-KG-dependent enzymes, modifying the endogenous cellular biochemical balance 15 . (nature.com)
- Traditionally, antifolates inhibit enzymes that are directly involved in the biosynthesis of purine and pyrimidine nucleotides. (aspetjournals.org)
- In addition to evidence of efficacy as a monotherapy, some HDAC inhibitors have been shown to inhibit tumor growth synergistically when administered together with ionizing radiation (IR) or with DNA-interacting cancer drugs in preclinical models ( 6 - 12 ). (pnas.org)
- In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inhibit xanthine oxidase are indicated for treatment of hyperuricemia and related medical conditions including gout. (wikipedia.org)
- Moreover, we report the identification of structural features required for kinase inhibition, co-crystal structures of CDK2 in complex with initial leads, and evidence for a selective inhibition of CDK2 in tumor cells. (aacrjournals.org)
- Kinemuchi H, Arai Y, Toyoshima Y, Tadano T, Kisara K. Studies on 5-fluoro-alpha- methyltryptamine and p-chloro-beta-methylphenethylamine: Determination of the MAO-A or MAO-B selective inhibition in vitro . (springer.com)
- Angiotensin converting enzymeinhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. (eurekaselect.com)
- Dipeptidyl peptidase-4 inhibitors are antidiabetic drugs used to improve glycaemic control. (eurekaselect.com)
- Objective: To assess the risk and pathomechanism of angioedema due to inhibition of dipeptidyl peptidase- 4 inhibitors when used as monotherapy and in combination with angiotensin converting enzymeinhibitors. (eurekaselect.com)
- Many drug molecules are enzyme inhibitors, so their discovery and improvement is an active area of research in biochemistry and pharmacology . (wikipedia.org)
- A dose reduction for Sutent to a minimum of 37.5 mg (GIST and RCC) or 25 mg (pNET) daily should be considered if Sutent must be co-administered with a strong CYP3A4 inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. (drugs.com)
- In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. (nih.gov)
- This review will summarize our knowledge about the function and structure of the enzyme, update the spectrum of inhibitors of the enzymatic activities of the NTPase/helicase and describe the different mechanisms by which the compounds act. (edu.pl)
- 4 Over the last several decades, our understanding of ACE inhibition has evolved from a theory based on simple hemodynamic effects of vasodilatation to beneficial effects on mechanisms throughout the cardiorenal and cardiovascular systems. (cmaj.ca)
- In particular, it deals with possible mechanisms of inhibition of Interleukin Converting Enzyme (ICE). (mit.edu)
- His research can be summarized as investigations of the molecular mechanisms of action, rational design, and syntheses of potential medicinal agents acting on enzymes and receptors. (whsmith.co.uk)
- Predicated on their type, these adjuvants may either promote higher degrees of the humoral immune system response or Entinostat reversible enzyme inhibition stimulate a combined mix of mobile and humoral immune system reactions. (sciencepop.org)
- The binding of sulfonamide inhibitor to a CA is linked to several protonation reactions, namely, deprotonation of the sulfonamide group, protonation of the active site zinc hydroxide and the compensating protonation-deprotonation of buffer. (sigmaaldrich.com)
- Inhibition of oncogenic mIDH1/2 represents an opportunity for therapeutic intervention. (nature.com)
- Both of these effects implicate the catalytic activity of EGFR and ErbB-2 in the development and maintenance of the neoplastic phenotype, suggesting that inhibition of this activity could provide a therapeutic opportunity in patients with tumors expressing either or both of these receptors. (aacrjournals.org)
- If and when that compound and others also show efficacy, that will give us definitive proof of the therapeutic potential of SIRT2 inhibition for HD. (massgeneral.org)
- Since RAS inhibitors are widely used in the clinical practice without serious side effects, they may represent a potential new therapeutic strategy against the progression of chronic liver diseases. (eurekaselect.com)
- Histone deacetylase (HDAC) inhibitors such as the phenyl hydroxamic acid PCI-24781 have emerged recently as a class of therapeutic agents for the treatment of cancer. (pnas.org)
- 11,12 However, concerns related to hyperkalemia risk and other risks with the use of RAAS inhibitors have contributed to sub-therapeutic dosing, discontinuation, and avoidance of RAAS inhibitors when clinically indicated. (ajmc.com)
- Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. (wikipedia.org)
- For example, enzymes in a metabolic pathway can be inhibited by downstream products. (wikipedia.org)
- Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). (nature.com)
- The present study was undertaken to test the hypothesis that an ACE inhibitor increases coronary blood flow and improves myocardial metabolic and contractile functions of ischemic myocardium. (biomedsearch.com)
- 49800. His main research interest is on enzyme inhibitors, and especially carbonic anhydrase inhibitors, of which he discovered several new classes in the last years. (benthamscience.com)
- Intrinsic thermodynamics of sulfonamide inhibitor binding to human carbonic anhydrases I and II. (sigmaaldrich.com)
- Carbonic anhydrase inhibitors. (uniprot.org)
- On the other hand, CV11974, an inhibitor of angiotensin II receptors, slightly increased coronary blood flow to 34 +/- 2 from 30 +/- 1 mL/100 g per minute. (biomedsearch.com)
- Angiotensin-II (AT-II) reportedly stimulates contractility and proliferation of the activated hepatic stellate cells, and increases the transforming growth factor-β (TGF-β) expression through angiotensin type-I receptors (AT1-R). Many studies have demonstrated that the clinically used angiotensin-converting enzyme inhibitors (ACE-I) and AT1-R blockers (ARB) significantly attenuated the liver fibrosis development in the experimental studies and clinical practice. (eurekaselect.com)
- Signs and symptoms of acetyl cholinesterase inhibitors - and their relationship to nicotinic and muscarinic receptors - are summarized in Figure 5 below. (cdc.gov)
- In response to a report of precancerous changes in the pancreases of rats and organ donors treated with the DPP-4 inhibitor sitagliptin, the United States FDA and the European Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-4 inhibitors with pancreatic cancer. (wikipedia.org)
- Ideally, specific inhibition of mIDH1 or mIDH2 would have few clinical side-effects, as no endogenous biochemistry would be disrupted by pharmacologic modulation. (nature.com)
- Many of these inhibitors are in clinical trials for patients with AML or solid tumors demonstrating the rapid advancement from the first report of the IDH1 mutation seven years ago to current late phase clinical trials. (nature.com)
- The value of renin-angiotensin-aldosterone inhibition in reducing mortality and morbidity among patients with heart failure and left ventricular systolic dysfunction has been well established in multiple large randomized clinical trials. (cmaj.ca)
- Given the important effects of ACE inhibitors on clinical outcomes, as shown in clinical trials, we need to know whether there are differences among the large number of ACE inhibitors currently being marketed (11 in the United States and 12 in Canada). (cmaj.ca)
- Indeed there are no large clinical trials comparing the efficacy of one ACE inhibitor with another to determine which one best improves survival. (cmaj.ca)
- Despite great research efforts and the resulting impressive number of high-affinity thrombin inhibitors identified, there is still only limited clinical use of some parenterally available preparations of thrombin inhibitors. (pnas.org)
- The reasons that render many inhibitors unattractive for clinical applications are manifold. (pnas.org)
- Clinical profile of angioedema with angiotensin-converting enzyme inhibition. (springer.com)
- PCI-24781 (formerly CRA-024781) is a broad-spectrum phenyl hydroxamic acid HDAC inhibitor currently being evaluated in phase I clinical trials in patients with neoplastic disease ( 3 ). (pnas.org)
- PCI-24781, along with other HDAC inhibitors also in clinical development, represent a promising class of anticancer therapy agents ( 4 , 5 ). (pnas.org)
- To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. (scielo.br)
- 13-15 As a result, there is a large gap between guideline recommendations and real-world clinical practice in the use of RAAS inhibitors. (ajmc.com)
- and (3) whether clinical outcomes are affected in patients who are prescribed doses below guideline recommendations or whose RAAS inhibitors are discontinued. (ajmc.com)
- Currently there are some NOX4 inhibitors drugs, so the study indicates its clinical potential and explains how they might act if they are used as a treatment in patients with hepatic fibrosis. (bio-medicine.org)
- In clinical trials, a single intravenous dose of peramivir, a sialic acid analogue and a selective inhibitor of neuraminidases produced by influenza A and B viruses, is effective and well tolerated in subjects with uncomplicated seasonal influenza virus infection. (medscape.com)
- As a result, the extent of inhibition depends only on the concentration of the inhibitor. (wikipedia.org)
- The experiment was carried out using the Beckman PACE system and steps were taken to determine (a) the migration profiles of angiotensin and its yielded peptides, (b) the minimal amount of angiotensin II detected, (c) the use of different electrolytes and (d) the concentration of inhibitor. (ox.ac.uk)
- Change the inhibitor concentration, which remains constant during reaction, with a slider. (wolfram.com)
- A well-characterised example of this is the ribonuclease inhibitor , which binds to ribonucleases in one of the tightest known protein-protein interactions . (wikipedia.org)
- Reversible inhibitors attach to enzymes with non-covalent interactions such as hydrogen bonds , hydrophobic interactions and ionic bonds . (wikipedia.org)
- Docking and molecular dynamics studies revealed that the three inhibitors made interactions with residues at the secondary binding site to phosphate, exclusive for PTP1B. (mdpi.com)
- X-ray structures of the inhibitor/Pim-1 binding complex reveal important salt-bridge and hydrogen bond interactions mediated by the compound's carboxylic acid and amino groups. (sigmaaldrich.com)
- There are several reasons that drugs can have negative interactions based on CYP enzymes. (proteopedia.org)
- We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2- a ]pyridine nucleus. (aacrjournals.org)
- Although considerable efforts are still devoted to these chemical families and their structurally related analogues, the identification of new structural classes of protein serine/threonine kinase inhibitors remains highly desirable. (aacrjournals.org)
- Herein we report that the aminoimidazo[1,2- a ]pyridine scaffold represents a new structural class of protein serine/threonine kinase inhibitors. (aacrjournals.org)
- The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2- a ]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways. (aacrjournals.org)
- Novel benzofuran-2-carboxylic acids, exemplified by 29, 38 and 39, have been discovered as potent Pim-1 inhibitors using fragment based screening followed by X-ray structure guided medicinal chemistry optimization. (sigmaaldrich.com)
- In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. (dtu.dk)
- Angiotensin-converting enzyme inhibition studies by natural leech inhibitors by capillary electrophoresis and competition assay. (ox.ac.uk)
- A competition assay using p-benzoylglycylglycylglycine and insect ACE established that LORF and IPEP fragments are natural inhibitors for invertebrate ACE. (ox.ac.uk)
- When cells RepSox reversible enzyme inhibition reached ~70% confluence, the tradition medium was changed with XF Assay moderate (Seahorse Bioscience), including 2 mM sodium pyruvate and 2.5 mM glucose for the OCR assay. (cdkkinase.com)
- Concerning the optimization of thrombin inhibitors, each cycle comprised synthesis of drug candidates, characterization of these compounds in a number of bioassays, and algorithmic processing of the data to generate or improve a predictive model that links compound structure and molecular properties, and which is used to design a new set of compounds. (pnas.org)
- Enzyme inhibitors also occur naturally and are involved in the regulation of metabolism . (wikipedia.org)
- 3. Combined pharmacokinetic/pharmacodynamic studies are required to assess the pharmacological relevance of either induction or inhibition of the enzymes involved in drug metabolism. (nih.gov)
- It has been suggested that angiotensin converting enzyme (ACE) may play a role in the metabolism of atrial natriuretic peptide (ANP), and that ANP may interfere with angiotensin-induced vasoconstriction. (biomedsearch.com)
- These studies in healthy subjects demonstrate no effect of local ACE inhibition on resting blood flow, or on the vasodilatation produced by ANP in the human forearm, and provide no evidence of a role of ACE in the metabolism of ANP in this vascular bed. (biomedsearch.com)
- However, it is also true that combination therapy using high doses of loop diuretics and ACE-inhibitors can entail harmful consequences for glomerular filtration function. (scielo.br)
- Nevertheless, several studies have pointed out that hypotension, as developing during unloading treatment with IV loop diuretics maintained for several days, can produce a more detrimental effect on renal hemodynamics and glomerular filtration, if an ACE-inhibitor therapy is also administered 15-17 . (scielo.br)
- Since intensive diuretic therapy is known to be capable of producing impaired renal blood supply and renal worsening from sodium and volume depletion in patients with CHF 18-20 , the attempt to detect any potential drug interaction between ACE inhibitors and diuretics in our CHF patient population has just been one of the aims of our study. (scielo.br)
- Dipeptidyl Peptidase-4 Inhibitor Induced Angioedema - An Overlooked Adverse Drug Reaction? (eurekaselect.com)
- Results: Both angiotensin converting enzyme and dipeptidyl peptidase-4 are major enzymes in the degradation pathway of bradykinin and substance P, and when inhibited pharmacologically - especially at the same time - the theoretical risk of angioedema is increased due to accumulation of vasoactive kinins. (eurekaselect.com)
- Angioedema is a rare but potentially serious complication of angiotensin-converting enzyme inhibitor (ACE) use. (ahajournals.org)
- This study aims to examine current knowledge on the occurrence, pathophysiology, and treatment of angioedema among patients who receive angiotensin-converting enzyme inhibitors. (springer.com)
- The pathophysiology of ACE-I-induced angioedema involves inhibition of bradykinin and substance P degradation by ACE (kininase II) leading to vasodilator and plasma extravasation. (springer.com)
- Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. (springer.com)
- In Entinostat reversible enzyme inhibition this paper, we hypothesized that formulating HBsAg in Montanide ISA 266 as a water-in-oil adjuvant may lead to enhanced cellular and humoral immune responses in comparison to the commercial HBsAg vaccine. (sciencepop.org)
- Because organelle Ca2+ homeostasis influences fundamentally cellular functions and death signaling, the IMD 0354 reversible enzyme inhibition central location of grp75 may represent an important control point of cell fate and pathogenesis. (plant-finder.com)
- a) Cellular distribution AZD6738 reversible enzyme inhibition of glycogen during appressorium development. (bioxorio.com)
- Percent enzyme inhibition shown by plant extracts with liver glucosidases. (hindawi.com)
- Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests . (wikipedia.org)
- Zeller AA, Barsky J. In vivo inhibition of liver and brain monoamine oxidase by l-isonicotinyl-2-isopropyl hydrazine. (springer.com)
- Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) have led a study published in PLoS One showing that the inhibition of a family member of NADPH oxidase enzyme, NOX4, plays an important role in liver fibrosis. (bio-medicine.org)
- The purpose of this study is measure the alterations in renal blood oxygenation after angiotensin II converting enzyme inhibition. (clinicaltrials.gov)
- Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, with additional benefits, such as cardiovascular and renal protection, in patients with diabetes. (springer.com)
- 2. We assessed the potential of the kallikrein-kinin system in mediating the cardio-and reno-protective effects of ACE inhibitors in rats with chronic renal failure (CRF) using ACE inhibitors, a kinin antagonist and an AII receptor antagonist. (nii.ac.jp)
- Publications] Masahiro, Kohzuki: 'Kinin and angiotensin II receptor antagonists in rats with chronic renal failure : the chronic effects on cardio-and reno-protection of angiotensin converting enzyme inhibitors. (nii.ac.jp)
- 1-6 Current evidence-based guidelines consider RAAS inhibitors as integral components in the management and treatment of patients with HF 7,8 and CKD 9,10 and of patients with diabetes and comorbid hypertension or renal impairment. (ajmc.com)
- Records from patients with sufficient data and without preindex end-stage renal disease (ESRD), who had one or more RAAS inhibitor prescriptions prior to the fixed index date of July 1, 2009, were examined (specific medications and their dose levels included in each dose category are listed in eAppendix Box 1 ). (ajmc.com)
- A protocol to follow the processing of angiotensin I into angiotensin II by rabbit angiotensin-converting enzyme (ACE) and its inhibition by a novel natural antagonist, the leech osmoregulator factor (LORF) using capillary zonal electrophoresis is described. (ox.ac.uk)
- BACKGROUND: Angiotensin-converting enzyme (ACE) produces angiotensin II, causing vasoconstriction of coronary arteries and reduction of coronary blood flow. (biomedsearch.com)
- Inhibition of angiotensin II production due to inhibition of ACE partially contributes to coronary vasodilation in the ischemic myocardium. (biomedsearch.com)
- One possible answer could be the following: Patients with the comorbidities of hypertension, diabetes and cardiovascular disease might fulfil the indication for the use of angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists . (bmj.com)
- Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. (bmj.com)
- Direct correlation between potency of the compounds as CYP51 inhibitors and their antiparasitic effect in TB and TC cells implies essential requirements for endogenous sterol production in both trypanosomes and suggests a lead structure with a defined region most promising for further modifications. (nih.gov)