Preclinical Drug Development | Scientific research info incl meetings, conferences, seminars, symposia,tradeshows,jobs,jobfairs, professional tips and more.
The preclinical pharmacology group provides support for drug discovery and drug development programs at ETC. The group develops establishes and validates in vitro and in vivo pharmacokinetic and metabolic methods to screen and evaluate small molecules and peptides for their drug-like properties.. The group also establishes in vivo disease models to validate potential drugable targets and to evaluate therapeutic properties of preclinical drug candidates.. ...
Seventh Wave Laboratories now offers a battery of gastrointestinal (GI) preclinical models to help clients to assess the behaviour of oral medications.
The clinical utility of proteasome inhibitors as treatment for multiple myeloma and non-Hodgkins lymphoma (NHL) has been validated with two parenterally administered agents: bortezomib, a dipeptide boronate that was approved by the FDA in 2003; and carfilzomib, a tetrapeptide epoxyketone that has shown promising activity in Phase 1 clinical trials. The clinical development of an orally bioavailable proteasome inhibitor would offer improvement in both dosing flexibility and patience convenience over intravenous (IV) administration. Furthermore, oral administration will allow a practical approach to investigating the affect of prolonged proteasome inhibition by repeated daily dosing in patients with advanced malignancies. Here we describe the preclinical pharmacology of PR-047, a tripeptide epoxyketone that was selected through a medicinal chemistry effort designed to find a selective inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome that combined the efficacy and safety of ...
TY - JOUR. T1 - Preclinical pharmacology, ocular tolerability and ocular hypotensive efficacy of a novel non-peptide bradykinin mimetic small molecule. AU - Sharif, Najam A.. AU - Li, Linya. AU - Katoli, Parvaneh. AU - Xu, Shouxi. AU - Veltman, James. AU - Li, Byron. AU - Scott, Daniel. AU - Wax, Martin. AU - Gallar, Juana. AU - Acosta, Carmen. AU - Belmonte, Carlos. PY - 2014/11/1. Y1 - 2014/11/1. N2 - We sought to characterize the ocular pharmacology, tolerability and intraocular pressure (IOP)-lowering efficacy of FR-190997, a non-peptidic bradykinin (BK) B2-receptor agonist. FR-190997 possessed a relatively high receptor binding affinity (Ki=27nM) and a high invitro potency (EC50=18.3±4.4nM) for inositol-1-phosphate generation via human cloned B2-receptors expressed in host cells with mimimal activity at B1-receptors. It also mobilized intracellular Ca2+ in isolated human trabecular meshwork (h-TM), ciliary muscle (h-CM), and in immortalized non-pigmented ciliary epithelial (h-iNPE) cells ...
The Preclinical Pharmacology Core is located in two contiguous labs (L4.244/L4.245) on the 4th floor of the Green Science Building (L Building) within the Biochemistry Department.. ...
Preclinical Drug Discovery () pe OKIAN.ro. Pret: 691.99 lei. These books provide theoretical, practical and troubleshooting guidelines on various aspects o
Molecules, Vol. 25, Pages 429: Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome Molecules doi: 10.3390/molecules25020429 Authors: Pető Kósa Fehér Ujhelyi Sinka Vecsernyés Szilvássy Juhász Csanádi Vígh Bácskay BGP-15 is a n...
In a study published in Nature Communications, researchers at Karolinska Institutet and Uppsala University in Sweden present a new drug candidate, which selectively kills dormant cells within a cancer tumour through starvation. These tumour cells, which are found in less oxygenated parts of solid tumours, are resistant to conventional treatments.
Challenge 1: Redesign Research Pipeline. Clinical trials have yet to reveal an effective therapy for most brain tumours. This harsh reality stems, in part, from an incomplete understanding of brain tumour biology and the existence of a disconnect between preclinical drug development and rigorous testing in the clinic. Each element of the brain tumour research pipeline, from basic neurobiology to clinical trials, requires careful scrutiny and increased investment, although the development of an overarching strategy that facilitates and promotes interdisciplinary research is equally important . This strategy would bring an end to the previous siloed organization of working practices, in which basic and clinical researchers performed their studies independently and collaborated only when laboratory research was judged to be ready for the clinic or when the laboratory is engaged to understand the reasons why a promising drug failed to achieve the expected level of efficacy in clinical trials. Much ...
The CryostaX® in vitro drug discovery and preclinical drug development test systems now include pooled Sprague-Dawley rat and CD-1 mouse hepatocytes.
If microchip systems that act like organs are ever going to really change preclinical drug development, its going to happen one experiment---and Big
Fig. 4. Mode of inhibition against PHD3 (left) where GSK1278863 IC50 values were plotted as a function of [α-KG]/Kmapp and fit to an equation for competitive inhibition. Determination of the dissociation half-life value (t1/2) for GSK1278863 from PHD3 by rapid dilution method (right). The yellow squares show the enzyme activity after dilution fit to an equation to determine the observed rate of recovery (kobs). Control reactions at 10x IC50 (black circles) and 0.1x IC50 (white squares) represent enzyme activity before dilution and after dilution if the compound was rapidly reversible. ...
Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing J
Membrane and protein traffic to the cell surface is mediated by partially redundant pathways that are difficult to perturb in ways that yield a strong phenotype. Such robustness is expected in a fine-tuned process, regulated by environmental cues, that is required for...
Caco-2 assays measure the ability of a drug to be absorbed from the gastrointestinal tract and thereby to evaluate whether the drug can be suitably dosed via an oral route. It also provides information regarding the ability of a compound to serve as a substrate for the P-glycoprotein (Pgp) efflux drug pump.. Caco-2 cells are intestinal epithelial tumor cells that form a polarized monolayer, a well-defined brush border on the apical surface and intercellular junctions when plated on a semipermeable membrane in a Transwell® dish.. ...
The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by L-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.
Citoxlab provides toxicity studies for new vaccine preclinical safety evaluation: immune response, reproductive toxicology, safety pharmacology, etc.
Certain anti-diabetic drugs increase this risk of bone fractures, particularly in postmenopausal women, severely limiting their treatment options.
Activating KRAS mutations are commonly seen in 40% to 50% of human CRC (13). Although the prognostic role of such mutations is controversial, it is evident that they are powerful positive predictors for resistance to treatment with anti-EGFR therapies, such as cetuximab or panitumumab (14, 15). Because of the central role for KRAS in EGFR and other receptor tyrosine kinase signaling pathways during CRC carcinogenesis (16), robust KRAS-specific treatments are desperately needed for effective CRC treatment. As such efforts have been widely unsuccessful to date (17), the development of novel therapeutic approaches for treatment of KRAS-mutant CRC is a critical unmet clinical need.. Despite the identification of many candidate drug compounds during preclinical discovery efforts, the subsequent rate of success through the clinical trial pipeline is abysmal (18). Traditional preclinical drug discovery platforms often rely on genetically undefined and highly passaged human tumor cell lines. The in ...
Enrich your medicines pipeline - Domainex provides a complete range of preclinical drug discovery services tailored to meet all your research needs
Preclinical pharmacokinetic models capable of predicting concentrations/exposure in vivo under different dosing schema can provide an invaluable tool for the rational design of clinical dosing protocols. The overall goals of the studies described herein were to design and evaluate the use of rational dosing protocols for vandetanib, docetaxel, and combinations of the two using pharmacokinetically directed dosing protocols that were reflective of exposures attainable in humans and that target antitumor and antiangiogenic responses. We utilized a PBPK model for docetaxel to develop dosing protocols that would allow us to examine the effects of standard docetaxel treatment versus a metronomic or antiangiogenic schedule of docetaxel. Pharmacokinetic data on vandetanib was used to determine a steady-state dose level that was reflective of human vandetanib exposure (32).. Preclinical testing is an integral part of the development of new therapeutics and new therapeutic strategies. With increasing ...
HOUSTON -- (March 15, 2010) -- The film Avatar isnt the only 3-D blockbuster making a splash this winter. A team of scientists from Houstons Texas Medical Center this week unveiled a new technique for growing 3-D cell cultures, a technological leap from the flat petri dish that could save millions of dollars in drug-testing costs. The research is reported in Nature Nanotechnology. The 3-D technique is easy enough for most labs to set up immediately. It uses magnetic forces to levitate cells while they divide and grow. Compared with cell cultures grown on flat surfaces, the 3-D cell cultures tend to form tissues that more closely resemble those inside the body. Theres a big push right now to find ways to grow cells in 3-D because the body is 3-D, and cultures that more closely resemble native tissue are expected to provide better results for preclinical drug tests, said study co-author Tom Killian, associate professor of physics at Rice. If you could improve the accuracy of early drug ...
Aberrant signaling through Fibroblast Growth Factor Receptors (FGFR) has been reported in multiple types of human cancers. FGFR4 signaling contributes to the development and progression of subsets of cancer: in approximately 10 percent of hepatocellular carcinoma (HCC), genetic amplification of FGF19, encoding an endocrine FGF ligand that activates FGFR4-KLB receptors, has been reported. In models with this alteration, FGF19-FGFR4 signaling is oncogenic and antagonism of the FGF19-FGFR4 axis has been shown to be efficacious suggesting that selective targeting of FGFR4 may be an effective strategy for malignancies with FGFR4 activation.. We describe the preclinical characterization of INCB062079 a potent and selective inhibitor of the FGFR4 kinase. In biochemical assays INCB062079 inhibited FGFR4 with low nM potency and exhibited at least 250-fold selectivity against other FGFR kinases and greater than 800-fold selectivity against a large kinase panel. This selectivity derives from the ability of ...
CBSET, a non-for-profit preclinical research institute dedicated to biomedical research, education and advancement of medical technologies, announced today that its scientists have published data and analyses (
A wide range of in vitro models are used in preclinical drug testing for the investigation of ADME-Tox properties of NCEs. The liver is the main organ with regards to ADME-Tox, wih over 500 different functions ...
OTTAWA, ON / ACCESSWIRE / May 6, 2020 / Tetra Bio-Pharma Inc. (Tetra or the Company) (TSXV:TBP)(OTCQB:TBPMF), a leader in cannabinoid-derived drug discovery and development, is pleased to announce that it has now completed the modifications to the nonclinical safety program of PPP003 to ensure the launch of a Phase 1 trial in healthy volunteers later this year and subsequently be able to initiate a Phase 2 trial in patients with COVID-19 immediately after.. The Company is not making any express or implied claims that its product has the ability to eliminate, cure or contain the Covid-19 (or SARS-2 Coronavirus) at this time. As with any new drug candidate, PPP003 has not been shown to be safe or effective in the prevention or treatment of inflammatory cytokine conditions. Dr. Melanie Kelly, Ph.D., Chief Scientific Officer, Tetra Bio-Pharma has read and approves of the scientific disclosure in this news release.. Tetras drug development program for PPP003 was adjusted to support a Clinical ...
Koen Dechering of TropIQ Health Sciences in the Netherlands is developing a high-throughput functional assay to identify new compounds that specifically block transmission of the malaria parasites to their vector hosts, which is a difficult stage to target, and to test candidate drugs. The assay incorporates luciferase- expressing parasites, which emit light as they develop in the mosquito midgut, along with barcoded chemical libraries. In Phase I, they tested several barcoding strategies and identified a bacterium that could be genetically modified to carry a unique barcode for identifying hit compounds selected in the screen. They also developed the luminescent reporter parasite to track transmission. In Phase II, they will further develop the assay for higher throughput, and screen compounds from the Tres Cantos Antimalarial Set and the MMV Validation, Malaria and Pathogen boxes. They will also use the assay to characterize the mechanisms of action of other candidate transmission-blocking ...
Posted By Carmen Drahl on Mar 21, 2010 , UPDATE April 2: If you read this coverage please tell us what you thought about it here or in the comments.. 1:26:15 PM: Im @ Moscone Ctr in San Fran. T minus half hour to unveiling of new drug candidate structures. #acsmedi #acs_sf. 1:37:35 PM: A hearty welcome to any readers of Totally Synthetic @Totsyn #acsmedi. 2:01:50 PM: 1st: Albert J. Robichaud-of Lundbeck-on Pfizers $PFE SAM-531, 5-HT6 antagonist for schizophrenia, Alzheimers #acsmedi #acs_sf. 2:02:53 PM: Alzheimers therapies today- palliative. Modulate eiether acetylcholine, glutamate #acsmedi #acs_sf. 2:04:58 PM: ~45 million ppl with ALzheimers worldwide- patients have probs w learning,memory, reasoning #acsmedi #acs_sf. 2:06:33 PM: 5HT6- 1 of 14 serotonin receptors- a G-protein coupled receptor #acsmedi #acs_sf. 2:07:00 PM: block 5HT6- boosts levels of glutamate, acetylcholine neurotransmission in brain areas assoc w/learning, memory #acsmedi #acs_sf. 2:09:37 PM: focus has been indole, ...
Although the scientific community continues to combat male bias in preclinical research, representation of women in late-phase clinical trials has improved markedly in recent years.21 The National Institutes of Health initiative to increase the use of female organisms and cells in preclinical research ensures that the scientific community as a whole will grow to fully address the health of both men and women. A major obstacle to the incorporation of female animals into studies, however, has been the belief that the rodent estrous cycle would render the study of these animals prohibitively expensive or difficult. Our study shows for the first time in a single large data set of physiological measurements that this belief is not accurate.. Our findings show that sex differences in CV among rats are small despite hormone fluctuations because of the estrous cycle. Moreover, for the majority of phenotypes, cohorts larger than typically used in preclinical research are required to detect the sex ...
A new drug candidate is more likely to be approved for use if it targets a gene known to be linked to the disease; a finding that can help pharmaceutical companies to focus their drug development efforts. Emily King and colleagues from AbbVie report these findings in a new study published Dec. 12 in PLOS Genetics.
Read how one laboratory created an automated drug discovery screening system to identify new drug candidates to fight bloodborne pathogens.
Cureline research team has adopted effective protocols for preparation of primary human cell lines from solid tumors, cancer blood, cancer bone marrow and normal tissues. The prepared primary cell cultures maintain their differential state and can be used as an in-vitro model system to study relevant disease changes and susceptibility to new drug candidates.
Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy.. ...
<p>Kenyan scientists are revealing the potential for traditional herbal remedies to lead to new drug candidates to treat of herpes and malaria.</p>
ROCKVILLE, Md.--(BUSINESS WIRE)-- Rexahn Pharmaceuticals, Inc. (NYSE Amex: RNN), a clinical stage pharmaceutical company developing and commercializing potential best in class oncology and CNS
Are you looking for all the latest preclinical research news for across the life sciences. Find preclinical research news here at BioTechniques.
Confidence Beyond Compliance. Regulatory agencies offer sponsors guidance and regulations on what data is required for a products development, but there is not always clarity on when these studies need to be completed in respect to an investigational products stage of development. Furthermore, while ICH guidelines provide structure to global non-clinical strategies, there are often nuances to regional study design and execution that should be considered. While non-clinical efforts are most often associated with the objective of reaching first-in-man studies, non-clinical programs run the lifecycle of the drug development process. PharmaLex assists its clients by working closely with them to carefully balance what is required for each stage of development and registration while considering the variables of time and cost.. PharmaLex works with clients to design a customized program that best suits the clients needs. We place and monitor the program focusing on the following:. ...
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Tissue Organ Bath System is widely used in preclinical safety studies - considered as a valuable tool for the elucidation of the mechanism of action.
Following successful preclinical safety/ toxiciology studies, Patrys advanced PAT-SM6 into a first-in-human clinical trial in melanoma patients.
IITRI has more than 40 years of experience in the preclinical development of novel therapeutics and vaccines to protect against infectious diseases. Our services include efficacy and potency evaluations, toxicology and safety assessments, as well as analysis of human clinical trial samples.
ARC 64176 is the first of a new class of benzoylpyrrole calcium channel activators. It was undergoing preclinical trials with Aventis Pharma (formerly Hoechst
RNAis road from the clinic to the marketplace for drugs has been a bumpy one with the failure of some of the fields earliest candidates.
Noile-Immune signs its second high profile agreement, the latest with Adaptimmune to combine the companies technology in pre-clinical studies for the treatment of cancer.
In vivo imaging is at the heart of preclinical research into cancer biology and treatment, with advances in technology delivering tools that are ever more powerful, accurate and easy-to-use.
HCS Pharma is a biotechnological startup focused on in vitro preclinical research development with a specialisation in cellular imagery : High Content Analysis (HCA) and High Content Screening (HCS ...
HCS Pharma is a biotechnological startup focused on in vitro preclinical research development with a specialisation in cellular imagery : High Content Analysis (HCA) and High Content Screening (HCS ...
Laromustine is an experimental sulfonylhydrazine prodrug used in late-stage clinical studies against acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). Despite initial promise for both indications, clinical trials for GBM have not been as successful as those for AML. To investigate methods for improving the effectiveness of laromustine in GBM and to learn more about the mechanism of action of laromustine, a chemical genetic screen will be conducted to identify agents that sensitize GBM cells to the anti-proliferative effects of laromustine. The library, which will include approximately 450 FDA-approved drugs, will be screened using a newly optimized high throughput assay based on the Click-iT EdU Microplate Assay kit (Molecular Probes). Optimization of the assay has required determining the proper cell seed density, drug concentration and incubation time, and fluorescent substrate concentration, among other variables. It was determined that low cell seed densities allow for maximal
On behalf of the National Center for Advancing Translational Sciences (NCATS), I invite BIO stakeholders to join us for our inaugural
We develop a flexible and computationally efficient approach for analyzing high-throughput chemical genetic screens. In such screens, a library of genetic mutants is phenotyped in a large number of stresses. Typically, interactions between genes and stresses are detected by grouping the mutants and …
XenoGesis Ltd. is a laboratory-based contract research organisation (CRO) specialised in preclinical drug metabolism & pharmacokinetics (DMPK), quantitative bioanalysis and expert interpretation.
9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacok
Definition of Secondary Liabilities in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Secondary Liabilities? Meaning of Secondary Liabilities as a finance term. What does Secondary Liabilities mean in finance?
Definition of Indirect Liabilities in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Indirect Liabilities? Meaning of Indirect Liabilities as a finance term. What does Indirect Liabilities mean in finance?
Due to the promising early results seen in patients with primary brain cancer, Reata has begun clinical trials of RTA 744 in patients who have other types of tumors (for example, lung or breast cancer) that have spread to the central nervous system (CNS). Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on developing novel treatments for cancer, inflammation, and neurodegenerative diseases. Reata is matching its clinical and preclinical drug development programs with a best-of-class drug discovery platform to identify small molecule chaperones that can induce proper folding of p53, SOD, and Tau, misfolded proteins that are involved in cancer and neurodegenerative disease.
Small-molecule microarrays composed of tens of thousands of distinct synthetic molecules, natural products, and their combinations/modifications provide a high-throughput platform for studying protein-ligand interactions. Immobilization of small molecule compounds on solid supports remains a challenge as widely varied small molecules generally lack unique chemical groups that readily react with singly or even multiply functionalized solid support. We explored two strategies for immobilizing small molecule compounds on epoxy-functionalized glass surface using primary-aminecontaining macromolecular scaffolds: bovine serum albumin (BSA) and amine-modified poly-vinyl alcohol (PVA). Small molecules with N-hydroxysuccinimide (NHS) groups were conjugated to BSA or amine-modified PVA. Small-molecule-BSA conjugates and small-molecule-PVA conjugates were subsequently immobilized on epoxy-functionalized glass slides through amine-epoxy reactions. Using an oblique-incidence reflectivity difference (OI-RD) ...
Cytotoxicity tests for high-throughput drug discovery.: Despite theoretical obstacles associated with performing cell-based assays in high-density formats (micr
Dr. Claire Le Pichon earned her B.A. degree from Cambridge University, U.K. and her Ph.D. in Biological Sciences from Columbia University in 2007 in the laboratory of Dr. Stuart Firestein, where her interest in neurodegenerative disease began while studying the function of the cellular prion protein PrPC. After her Ph.D., Dr. Le Pichon joined the Translational Neuroscience group at Genentech, where she worked on preclinical drug development for multiple neurodegenerative disease pipeline targets, using mouse models of disease. She was recruited as an Investigator to the NICHD in 2016. Her laboratory employs a multidisciplinary approach including mouse genetics, wide-scale imaging of whole brain tissue, next generation sequencing, and behavior to investigate the early events underlying the onset and progression of neurodegenerative disease. ...
TY - JOUR. T1 - Preclinical assessment of infant formula. AU - Lönnerdal, Bo. PY - 2012/6. Y1 - 2012/6. N2 - Infant formulas are the sole or predominant source of nutrition for many infants and are fed during a sensitive period of development and may therefore have short- and long-term consequences for infant health. Preclinical safety assessment therefore needs to include both short-term and long-term studies in animals. It is recommended that procedures are instituted by which experts may serve as independent scientists for companies developing novel products, without having their integrity compromised, and later serve the legislative institutions. A two-level assessment approach to determine the potential toxicity of a novel ingredient, its metabolites, and their effects in the matrix on developing organ systems has been suggested by IOM. This appears reasonable, as novel ingredients can be of different levels of concern. The use of modern methods in genomics and proteomics should be ...
AKT is frequently deregulated in cancer, making it an attractive anticancer drug target. CCT128930 is a novel ATP-competitive AKT inhibitor discovered using fragment-and structure-based approaches. It is a potent, advanced lead pyrrolopyrimidine compound exhibiting selectivity for AKT over PKA, achieved by targeting a single amino acid difference. CCT128930 exhibited marked antiproliferative activity and inhibited the phosphorylation of a range of AKT substrates in multiple tumor cell lines in vitro, consistent with AKT inhibition. CCT128930 caused a G(1) arrest in PTEN-null U87MG human glioblastoma cells, consistent with AKT pathway blockade. Pharmacokinetic studies established that potentially active concentrations of CCT128930 could be achieved in human tumor xenografts. Furthermore, CCT128930 also blocked the phosphorylation of several downstream AKT biomarkers in U87MG tumor xenografts, indicating AKT inhibition in vivo. Antitumor activity was observed with CCT128930 in U87MG and ...
Antibody drug conjugate (ADC) comprise of a monoclonal antibody and cytotoxic payload conjugated by a linker. The antibody is purposed to deliver the payload to the target located on the cancer cell. The payload is typically a highly potent small molecule, which should be released from the carrier antibody inside the tumour cell. The number of the released but differently conjugated small molecules is affected by the used conjugation method and strategy.
Read A simple high throughput assay to evaluate water consumption in the fruit fly, Scientific Reports on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
MNP001 is a newly synthesized 3-carbamyl-4-methylpyrrole analog with dual pharmacophores simultaneously to inhibit phosphodiesterase type 4 (PDE4) and to antagonize L-type calcium channels. The physicochemical properties of MNP001, including solubility, pKa, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. The preclinical pharmacokinetic parameters were determined in an in vivo rat model and the metabolic pathways of MNP001 were characterized by incubating the compound in vitro in rat or human microsomes/supersomes cocktails. MNP001 was found to have a low solubility in simulated intestinal fluid but a high solubility in simulated gastric fluid. MNP001 is a highly lipophilic compound with a Log P value greater than 4. MNP001 was highly bound to the plasma protein and had an uneven partition between red blood cells and plasma. MNP001 exhibited a rapid absorption, broad distribution, slow systemic clearance and a low but
The PI3K pathway, which is commonly altered in numerous cancers (Liu et al., 2009a), has been identified as a promising target for the treatment of malignancies. Components of this signaling pathway, such as PI3K or mTOR, can be targeted by small molecules, and several inhibitors specific for one of these two kinases are being evaluated in patients (Engelman, 2009). Inhibitors of mTOR (mTORC1), referred to as rapalogs, have been approved for the treatment of cancers, and numerous dual PI3K/mTOR inhibitors are currently in clinical trials (Benjamin et al., 2011).. Preclinical pharmacokinetic studies provide key parameters during the discovery and the early stages of development of a compound. These parameters help to assess whether sufficient exposure can be achieved in further animal studies (efficacy and toxicology) and also are used to predict pharmacokinetic properties in humans. In addition, when integrated with efficacy data in PK-PD models, they can be used to estimate efficacious and ...
Rationale: Despite four decades of intense effort and substantial financial investment, the cardioprotection field has failed to deliver a single drug that effectively reduces myocardial infarct size in patients. A major reason is insufficient rigor and reproducibility in preclinical studies. Objective: To develop a multicenter randomized controlled trial (RCT)-like infrastructure to conduct rigorous and reproducible preclinical evaluation of cardioprotective therapies. Methods and Results: With NHLBI support, we established the Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR), based on the principles of randomization, investigator blinding, a priori sample size determination and exclusion criteria, appropriate statistical analyses, and assessment of reproducibility. To validate CAESAR, we tested the ability of ischemic preconditioning (IPC) to reduce infarct size in three species (at two sites/species): mice (n=22-25/group), rabbits (n=11-12/group), and pigs ...
In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.
Drug Discovery Today is a review journal, published as monthly 12 double issues. The journal covers the whole of the preclinical drug discovery process, from target identification and validation, through hit identification, lead identification and optimisation, though to candidate selection. The reviews are at the cutting edge of the science underpinning drug discovery, written by experts in their respective fields and cover all aspects of drug discovery from state-of-the-art genomic and proteomic approaches to target identification, through the most innovative computational approaches drug design, the science driving medicinal chemistry and the translation of these sciences to therapies
Drug Discovery Today is a review journal, published as monthly 12 double issues. The journal covers the whole of the preclinical drug discovery process, from target identification and validation, through hit identification, lead identification and optimisation, though to candidate selection. The reviews are at the cutting edge of the science underpinning drug discovery, written by experts in their respective fields and cover all aspects of drug discovery from state-of-the-art genomic and proteomic approaches to target identification, through the most innovative computational approaches drug design, the science driving medicinal chemistry and the translation of these sciences to therapies
Technology Networks is an internationally recognised publisher that provides access to the latest scientific news, products, research, videos and posters.
Downloadable! This paper studies the interdependence of households? financial assets and liabilities in European countries. Most studies treat household liabilities as negative assets and relate households? decisions to their net wealth. However, the components of net wealth, i.e. financial liabilities, financial assets and real assets are very heterogeneous across households. The assumption of similar consumption behaviour among households with the same net wealth but different wealth components is implausible. This paper raises another question, namely whether households consider their indebtedness when they make decisions about their financial assets. The implication of household indebtedness for household behaviour is an important topic as household debt volumes have increased markedly in developed countries over the last three decades. There is a long list of research about household borrowing and the financial vulnerability of indebted households, but there has been less discussion about whether
Lundbeck divests preclinical research programs Two programs outside Lundbecks areas of focus are transferred to MindImmune Therapeutics, Inc. H. Lundbeck A/S (Lundbeck) further focuses its preclinical research pipeline with the divestment of two research programs to biotech company MindImmune Therapeutics, Inc. (MindImmune). In exchange for the programs, Lundbeck receives an equity interest in MindImmune as well as milestone payments and royalties according to the progression of the programs. The agreement follows Lundbecks strategy of focusing its efforts within four disease areas; depression, schizophrenia, Alzheimers disease and Parkinsons disease, for which the programs are not relevant. Per its strategy Lundbeck itself has therefore not prioritized further development of the programs, but the agreement ensures that these potential new treatments will now be brought forward. There will be no costs for Lundbeck associated with the future development of the programs. We focus on ...
Comparative Biosciences, Inc. provides expert scientific resources and quality service to all sectors of the biomedical and biopharmaceutical community. We offer extensive experience in GLP and non-GLP preclinical toxicology, efficacy, pharmacology, pharmacokinetics-pharmacodynamics, histopathology and safety studies on all laboratory species.
Virtual drug screening is one of the most widely used approaches for finding new drugs candidates. The process consists in selecting one or more chemical compounds with the highest binding free energy to target proteins. Given that the empirical space of chemical compounds is extremely large and estimated to has over 50 millions of them, finding the most effective drug becomes computationally challenging. Furthermore, the vast majority of proteins still lack the experimentally obtained 3D structures required for most of the molecular computer tools available, making it impossible to calculate their binding free energies with chemical compounds. In view of this, the aim of our study is to asses the effectiveness of the Autodock Vina tool in a large environments with unstructured proteins, those without defined 3D structure. The ultimate goal is to enable a fast and efficient virtual drug screening in such an environments, and to apply it for discovery of a new drug candidates.. ...
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The aim of the present study is to test the effect of a 15-day treatment with donepezil on a mixed battery associating cognitive assessment, imaging and neurophysiological tests in healthy volunteers.. This multicenter, randomized, placebo-controlled, cross-over study is double-blind controlled and is conducted in 3 centers located in France (Lille, Marseille and Toulouse).. 18-30 years old, healthy volunteers, without any neurological or psychiatric impairment, will complete 2 test sessions in a randomized order: one with a 15-day treatment with donepezil, the other with placebo, and will be submitted to a mixed battery during the 14th and 15th day of the treatment. The primary outcome of the study will be based on cognitive assessment, imaging parameters and neurophysiological parameters. ...
Eventbrite - Michigan Association of OWI Attorneys & State Bar of Michigan Marijuana Law Section presents Drug Evaluation and Classification Course - Friday, May 8, 2020 | Saturday, May 9, 2020 at The James B. Henry Center for Executive Development, Lansing, MI. Find event and ticket information.
In the absence of an efficient vaccine, prevention of HIV transmission remains the primary and economically feasible infection prevention method available to da...
Following publication of the original article [1], the authors found an error in Figure 3. The middle panel of Figure 3a was inadvertently duplicated.
Atomwise announced the launch of a ten billion compound AI-powered virtual drug screening initiative, the 10-to-the-10 program, in collaboration with Enamine, the worlds largest chemical supplier. The initiative aims to dramatically increase the discovery of safer small molecule drugs to treat pediatric cancers.. Atomwise will use its patented AI virtual screening technology to evaluate the binding of billions of drug-like molecules to cancer target proteins, and Enamine will provide support and access to a virtual library of ten billion small molecule compounds. The research will be directed by the needs of innovators in cancer research at leading universities.. Cancer is diagnosed in more than 15,000 children and adolescents each year. Many cancers do not have effective treatments and for those that do, it is estimated that 80% have serious adverse effects that impact long-term health. Therefore, new oncology drugs are needed. The 10-to-the-10 program will search for novel drug candidates by ...
In 2009, the same development team created Adam, a robot scientist that became the first machine to independently discover new scientific knowledge. They used the knowledge from that experiment to create Eve with the purpose of speeding up the drug discovery process and make it more economical. In the published study, the researchers discuss describe how the robot is able to identify promising new drug candidates for malaria and other neglected tropical diseases, such as African sleeping sickness and Chagas disease.. Neglected tropical diseases are a scourge of humanity, infecting hundreds of millions of people, and killing millions of people every year, said Steve Oliver, a professor from the Cambridge Systems Biology Centre and the Department of Biochemistry at the University of Cambridge. We know what causes these diseases and that we can, in theory, attack the parasites that cause them using small molecule drugs. But the cost and speed of drug discovery and the economic return make them ...
REGENXBIO total liabilities from 2014 to 2020. Total liabilities can be defined as the total value of all possible claims against the corporation.
Most preclinical studies that aim to prove the antistroke efficacy of candidate drugs are performed in experimental settings bearing little-if any-resemblance to clinical reality, which is a possible reason for several neuroprotective drug failures (36,37). Potential causes of this lack of success include use of preclinical drug administration paradigms not achievable at the clinic level (e.g., drug administration before or very shortly after stroke, intracerebroventricular injections, and too-high doses of the candidate drugs (38)), efficacy experiments performed using animal models that lack common comorbidities of stroke patients, such as diabetes and hypertension (36), and finally, nearly all rodent stroke studies are performed in young animals, whereas most stroke patients are elderly (39).. Our goal in the current study was to determine the potential antistroke efficacy of a DPP-4 inhibitor therapy by mimicking the likely clinical scenario of an obese type 2 diabetic patient receiving this ...
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PRECLINICAL PHARMACOLOGICAL STUDIES OF ANTITUMOR AND ANTI-HIV AGENTS NIH GUIDE, Volume 23, Number 3, January 21, 1994 RFP AVAILABLE: NCI-CM-57199-12 P.T. 34 Keywords: Pharmacology Chemotherapeutic Agents National Cancer Institute The Developmental Therapeutics Program (DTP), Division of Cancer Treatment, is soliciting organizations having the necessary experience, scientific and technical personnel, and facilities to conduct a series of preclinical pharmacokinetic and other pharmacology studies in non-disease bearing animals on agents having demonstrated antitumor or anti-HIV activity and considered by DCT to merit further development. The studies to be performed will include: the development of methodology for the quantitative measurement of test agents and/or metabolites in animal body fluids and tissues; stability studies of test agents in biological fluids; plasma protein binding determinations; characterization of in vivo plasma concentration-time profiles and calculation of relevant ...
Zhang L, Balan G, Barreiro G, Boscoe BP, Chenard LK, Cianfrogna J, Claffey MM, Chen L, Coffman KJ, Drozda SE, Dunetz JR, Fonseca KR, Galatsis P, Grimwood S, Lazzaro JT, Mancuso JY, Miller EL, Reese MR, Rogers BN, Sakurada I, Skaddan M, Smith DL, Stepan AF, Trapa P, Tuttle JB, Verhoest PR, Walker DP, Wright AS, Zaleska MM, Zasadny K, Shaffer CL. Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): a highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator. J Med Chem. 2014 Feb 13; 57(3):861-77 ...
Next, an unlabeled compound was analyzed using the kinetic probe competition assay. The reaction contained fluorescent tracer 178 and the indicated concentrations of staurosporine, an unlabelled ABL-binder. The reaction was started by adding Tb-labelled ABL resulting in a signal increase for the trace without competitor (Fig. 3, grey). In contrast, the signal in presence of the competitor is lower the higher its concentration, and the initial signal increase is followed by a decrease in signal over time. The latter indicates that due to slower binding kinetics the competitor equilibrates more slowly than the tracer. ...
Herein are a collection of studies that build on our existing knowledge of estrogen actions in the brain. We extend the efforts of current neuroprotective strategies by demonstrating that estrogenic molecules promote cell survival mechanisms governed by neuronal mitochondria. Estrogen (E2, 17beta-estradiol) protects neurons from a series of age-related risk factors for developing Alzheimer s disease (AD) supported by basic science, clinical, and epidemiological data. However, there exists a window of opportunity for E2 as a preventive therapy and our findings are not intended for hopeful treatments of pre-existing pathologies but rather to support the proposed healthy-cell bias therapeutic approach (Brinton 2005). Our preclinical pharmacology research work covers biochemistry, molecular biology and cell imaging of rodent brain. Controlled in vitro and in vivo studies are organized under four specific aims that test our hypotheses in brain tissues with a focus on the hippocampus and cortex ...
Gliobastoma multiforme (GBM) is an aggressive malignant form of brain tumour for which effective therapies are limited. Genetically engineered mouse models (GEMMs) harbouring mutations in components of the main signalling pathways that are altered in human GBM - including the receptor tyrosine kinase (RTK)-RAS- phosphoinositide-3-kinase (PI3K) pathway - are available. However, these GEMMs display a long latency to tumorigenesis and advanced tumour heterogeneity, which represents a challenge in preclinical drug testing. In this study, Zoë Weaver Ohler and colleagues developed an orthotopic and tractable mouse model of GBM by transplanting brain tumour cells derived from GBM-GEMMs into the brain (orthotopically) of syngeneic mice (non-transgenic wild-type mice with identical genetic backgrounds and intact immune systems). This model develops GBM with features of the human disease, including high vascularisation and aggressive invasion of surrounding tissues, and thus was used to test the effects ...
[email protected] Course Description. This three-credit course is intended to help Master of Science students in the Preclinical Pharmacology Track of the existing MBS Program understand the skills required to integrate pharmacotherapeutic and pathophysiologic concepts through use of clinical case studies. The course will be conducted in an interactive small group format with no more than 15 students per class. The course will consist of seven three-hour sessions, in which clinical cases will be presented and discussed. Prior to each class session, students will be provided with the descriptions of the cases assigned for that session as well as specific questions relating to each assigned case that will be discussed in class. Using reliable information sources (including two free online textbooks), students will be expected to formulate responses to the case questions in advance of each class session, and to engage in interactive discussions of the questions during the class period. ...
Object. Determining the efficacy of a drug used in experimental traumatic brain injury (TBI) requires the use of one or more outcome measures such as decreased mortality or fewer neurological and neuropsychological deficits. Unfortunately, outcomes in these test batteries have a fairly large variability, requiring relatively large sample sizes, and administration of the tests themselves is also very time consuming. The authors previously demonstrated that experimental TBI and human TBI induce mitochondrial dysfunction. Because mitochondrial dysfunction is easy to assess compared with neurobehavioral endpoints, it might prove useful as an outcome measure to establish therapeutic time windows and dose-response curves in preclinical drug testing. This idea was tested in a model of TBI in rats.. Methods. Animals treated with the selective N-type voltage-sensitive calcium channel blocker Ziconotide (also known as SNX-111 and CI-1009) after cortical impact displayed significant improvement in brain ...
|p||em|Reaxys Medicinal Chemistry enables scientists to explore new drug candidates through a comprehensive database with new search features, refined user-interface and integration with Reaxys|/em||/p|
We evaluated a multiplexed PCR panel for the detection of 16 bacterial, viral, and fungal pathogens in cerebrospinal fluid. Panel results were compared to routine testing, and discrepancies were resolved by additional nucleic acid amplification tests or sequencing. Overall, the positive and negative agreements across methods were 92.9% and 91.9%, respectively. ...