• Investigational Prodrug
  • Tenofovir alafenamide (TAF), an investigational prodrug of tenofovir, did not accumulate in primary osteoblasts (bone-forming cells) more than in peripheral blood mononuclear cells (PBMCs) and had no cytotoxic effects in osteoblasts at concentrations that would be used in humans . (natap.org)
  • nontoxic
  • The bacterial and yeast cytosine deaminases ( 9 , 10 ) convert the nontoxic prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), which is widely used in the treatment of a range of cancers, including colorectal and breast cancers ( 11 , 12 ). (aacrjournals.org)
  • Note 2: Prodrugs can thus be viewed as drugs containing specialized nontoxic protective groups used in a transient manner to alter or to eliminate undesirable properties in the parent molecule. (wikipedia.org)
  • vivo
  • The success of enzyme/prodrug cancer therapy is limited by the uncertainty in the delivery of the enzyme in vivo . (aacrjournals.org)
  • Here, for the first time, we report on the in vivo detection of a drug-activating enzyme functionalized with multimodal magnetic resonance (MR) and optical imaging reporters to provide image-guided delivery of prodrug. (aacrjournals.org)
  • therapeutic
  • The present invention provides amphiphilic prodrugs comprising a therapeutic compound conjugated to an PEG-oligomer/polymer and methods for using said prodrugs to enable oral drug delivery and/or delivery of drugs across the blood brain barrier into the central nervous system. (google.fr)
  • 7. The prodrug of claim 1 wherein the therapeutic compound comprises etoposide. (google.fr)
  • 8. The prodrug of claim 1 wherein the therapeutic compound comprises a etoposide analog which retains some or all of the therapeutic activity of etoposide. (google.fr)
  • 9. The prodrug of claim 1 wherein the therapeutic compound is derivatized by 1, 2, 3 or 4 of the polyethylene glycol oligomer(s). (google.fr)
  • 10. The prodrug of claim 1 which, when delivered via the oral route of administration to treat a mammalian subject having a disease condition responsive to the therapeutic compound, provides a therapeutically effective dose of the therapeutic compound to the blood. (google.fr)
  • Many therapeutic agents are manufactured and administered in prodrug forms. (mdpi.com)
  • Type IA prodrugs refer to those that are converted at the cellular targets of therapeutic actions, whereas Type IB prodrugs' conversion occurs in the primary metabolic tissues such as liver, gut, or lung. (mdpi.com)
  • As disclosed previously, we are planning to develop KP511 as an extended-release prodrug product candidate that could offer the potential to deter certain common methods of abuse while providing the same pharmacokinetic and therapeutic effect as existing hydromorphone products when taken as intended. (cnbc.com)
  • With this capability, prodrug administration can be timed so that the enzyme concentration is high in the tumor and low in systemic circulation and normal tissue, thereby minimizing systemic toxicity without compromising therapeutic efficiency. (aacrjournals.org)
  • Type II prodrugs are bioactivated extracelluarly, either in the milieu of GI fluids (Type IIA), within the systemic circulation and/or other extracellular fluid compartments (Type IIB), or near therapeutic target tissues/cells (Type IIC), relying on common enzymes such as esterases and phosphatases or target directed enzymes. (wikipedia.org)
  • moiety
  • 6. The prodrug of claim 1 wherein the salt-forming moiety is selected from the group consisting of: ammonium, carboxylate, phosphate, sulfate and mesylate. (google.fr)
  • 15. The prodrug of claim 14 wherein one or more of the polyethylene glycol oligomer(s) comprises a salt-forming moiety. (google.fr)
  • molecules
  • The tremendous transport capacity and organ specificity of enterohepatic circulation combined with versatile derivatization possibilities, rigid steroidal backbone, enantiomeric purity, availability, and low cost have made bile acids attractive tools in designing pharmacological hybrid molecules and prodrugs with the view of improving intestinal absorption, increasing the metabolic stability of pharmaceuticals, specifically targeting drugs to organs involved in enterohepatic circulation, as well as sustaining therapeutically reasonable systemic concentrations of active agents. (mdpi.com)
  • Classifications
  • In conclusion, the new system of classification will add to existing knowledge of prodrug classifications, and will provide improved insight into the contributory roles of both prodrug and active drug in the product's efficacy and safety, and their risk-benefit assessment. (mdpi.com)
  • compound
  • The Mixed-Type compound can be further distinguished as a Parallel Mixed-Type or Sequential Mixed-Type prodrug depending on the conversion processes that proceed with, either in concurrent or in sequential steps. (mdpi.com)
  • The half-life of the parent compound was prolonged after intragastric administration of prodrug 3 , which was found to be a superior prodrug candidate for increasing myocardial contractility. (mdpi.com)
  • A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug. (wikipedia.org)
  • However, terfenadine was discovered to be the prodrug of the active molecule, fexofenadine, which does not carry the same risks as the parent compound. (wikipedia.org)
  • Loratadine, another non-sedating antihistamine, is the prodrug of desloratadine, which is largely responsible for the antihistaminergic effects of the parent compound. (wikipedia.org)
  • therapy
  • This review focuses on the prodrugs used in suicide gene therapy. (hindawi.com)
  • Both prodrugs and their activated species should have good distributive properties, so that the resulting bystander effects can maximize the effectiveness of the therapy, since gene transduction efficiencies are generally low. (hindawi.com)
  • A total of 42 prodrugs explored for use in suicide gene therapy with 12 different enzymes are discussed, particularly in terms of their physiocochemical properties. (hindawi.com)
  • It is expected that continued studies to optimize the bystander effects and other properties of prodrugs and the activated species they generate will contribute to improvements in the effectiveness of suicide gene therapy. (hindawi.com)
  • These preclinical studies show the feasibility of using a MR-detectable prodrug enzyme to time prodrug administration in enzyme/prodrug cancer therapy. (aacrjournals.org)
  • bystander
  • Many of the early antimetabolite-based prodrugs provide very polar activated forms that have limited abilities to diffuse across cell membranes, and rely on gap junctions between cells for their bystander effects. (hindawi.com)
  • This review concentrates on bystander effects and drug development with regard to these enzyme prodrug combinations, namely herpes simplex virus thymidine kinase (HSV-TK) with ganciclovir (GCV), cytosine deaminase (CD) from bacteria or yeast with 5-fluorocytodine (5-FC), and bacterial nitroreductase (NfsB) with 5-(azaridin-1-yl)-2,4-dinitrobenzamide (CB1954), and their respective derivatives. (mdpi.com)
  • active drug
  • In this paper, a new classification system for prodrugs is proposed to provide useful information about where in the body a prodrug is converted to the active drug. (mdpi.com)
  • Compounds that are weak or inactive until the body transforms them into an active drug are called prodrugs , and this is the first situation that I can think of where a legal prodrug has been found for an illegal drug. (mindhacks.com)
  • Conversion of the prodrug by residual enzyme in normal tissues may lead to toxicity if the prodrug is injected too early, and to low tumor concentrations of the active drug if the prodrug is injected too late, because the enzyme concentration can decrease due to clearance or proteolytic degradation. (aacrjournals.org)
  • derivatives
  • Liposomal prodrugs including these specific derivatives of camptothecin restrained by a liposomal delivery system are also described. (google.com)
  • This article briefly describes bile acid transport proteins involved in enterohepatic circulation, summarizes the key factors affecting on the transport by these proteins, and reviews the use of bile acids and their derivatives in designing prodrugs capable of exploiting the bile acid transport system. (mdpi.com)
  • optimize
  • Imaging the tissue pharmacokinetics of a drug-activating enzyme would therefore be ideal to optimize the timing of prodrug delivery. (aacrjournals.org)
  • wherein
  • 2. The prodrug of claim 1 wherein the straight or branched PEG segment consists of from 2 to 20 polyethylene glycol units. (google.fr)
  • 5. The prodrug of claim 1 wherein the polyethylene glycol oligomer has a number of polyethylene glycol units selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, and 9. (google.fr)
  • 2. The liposomal prodrug of claim 1 , wherein R 1 is a linear C 2 -C 4 alkyl group or C 6 -C 15 alkyl group when R 2 is H and R 1 is a linear C 1 -C 15 alkyl group when R 2 is NH 2 or NO 2 . (google.com)
  • 3. The liposomal prodrug of claim 1 , wherein R 1 is a linear C 2 -C 15 alkenyl group or a C 2 -C 15 epoxy group. (google.com)
  • 4. The liposomal prodrug of claim 2 , wherein R 2 is NH 2 . (google.com)
  • 7. The liposomal prodrug of claim 2 , wherein R 1 is a linear methyl, ethyl or propyl group and R 2 is NH 2 . (google.com)
  • 8. The liposomal prodrug of claim 1 , wherein R 1 is a C 3 -C 8 cycloalkyl group and R 2 is NH 2 . (google.com)
  • 10. The liposomal prodrug of claim 1 , wherein said delivery system comprises at least one of cholesterol and phospolipids. (google.com)
  • 13. A method for treating cancer in a patient comprising administering a composition comprising an effective amount of the liposomal prodrug of claim 1 , wherein said cancer is responsive to said composition. (google.com)
  • absorption
  • Prodrugs are useful in that they can be used to avoid negative physiological effects associated with the absorption of standard drugs. (wikibooks.org)
  • drugs
  • Prodrugs are a new class of drugs that, upon administration, are inactive. (wikibooks.org)
  • The bioconversion of the prodrugs to their active parent drugs is by way of enzyme activity of hydrolases. (wikibooks.org)
  • Probably the most commonly used illicit prodrug is heroin, which is metabolised into morphine in the body, but both are Class A drugs in the UK so there's no legal benefit to having one rather than the other. (mindhacks.com)
  • KemPharm utilizes its LAT platform technology to generate improved prodrug versions of FDA-approved drugs in the high need areas of pain, ADHD and other CNS disorders. (cnbc.com)
  • 4.7 Lipophilic Prodrugs of Benzamidine Drugs. (wiley.com)
  • administration
  • CORALVILLE, Iowa, May 10, 2016 (GLOBE NEWSWIRE) -- KemPharm, Inc. (NASDAQ:KMPH), a clinical-stage specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs, today announced that KP511, KemPharm's prodrug of hydromorphone, has been granted "Fast Track" designation by the U.S. Food and Drug Administration (FDA). (cnbc.com)
  • KemPharm believes that this proprietary design offers the potential to restrict the release of the active hydromorphone component until the prodrug is metabolized following oral administration. (cnbc.com)
  • The optimal time window for prodrug administration was determined to be 24 h, at which time the enzyme continued to show high enzymatic stability in tumors but was biodegraded in the liver. (aacrjournals.org)
  • Steps
  • A Mixed-Type prodrug is one that is bioactivated at multiple sites, either in parallel or sequential steps. (wikipedia.org)
  • body
  • The reasons for this type of formulation may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better absorbed by the body or has superior pharmacokinetics (e.g., lisdexamphetamine). (wikipedia.org)
  • stages
  • It summarizes current experiences and strategies for the rational design of prodrugs, beginning at the early stages of the development process, as well as discussing organ- and site-selective prodrugs. (wiley.com)
  • processes
  • Processes for making these prodrugs and for using them in cancer treatment are also disclosed. (google.com)
  • A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. (wikipedia.org)
  • delivery
  • This study shows the use of noninvasive magnetic resonance (MR) and optical imaging to image the delivery of a prodrug enzyme. (aacrjournals.org)
  • The delivery of a multimodal imaging reporter functionalized prodrug enzyme, cytosine deaminase, was detected by MR and optical imaging in MDA-MB-231 breast cancer xenografts. (aacrjournals.org)
  • 6 Prodrugs Designed to Target Transporters for Oral Drug Delivery ( Mark S. Warren and Jarkko Rautio ). (wiley.com)
  • 7 Topical and Transdermal Delivery Using Prodrugs: Mechanism of Enhancement ( Kenneth Sloan, Scott C. Wasdo, and Susruta Majumdar ). (wiley.com)
  • 8 Ocular Delivery Using Prodrugs ( Deep Kwatra, Ravi Vaishya, Ripal Gaudana, Jwala Jwala, and Ashim K. Mitra ). (wiley.com)
  • found
  • Prodrugs 3 - 5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. (mdpi.com)