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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 ...
If microchip systems that act like organs are ever going to really change preclinical drug development, its going to happen one experiment---and Big
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.. ...
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 ...
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 ...
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 ...
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.
<p>Kenyan scientists are revealing the potential for traditional herbal remedies to lead to new drug candidates to treat of herpes and malaria.</p>
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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
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.
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 ...
CBSET is a recognized leader in preclinical research, helping sponsors around the globe accelerate the development of innovative therapeutics.
Use humanized mice as in vivo tools for mimicking human pathological conditions and diseases, and for conducting preclinical research.
I have a question regarding a jump in TA using 2014 chemicals and 2015 chemicals. I received replacement chemicals for my TF-100 kit yesterday. I ran the the usual tests today: TC,FC,CC,TA,pH with the new chemicals. New chemicals readings: TC: 5.0 FC: 0 CC: 5.0 TA: 170 pH: 7.2 I was surprised at the jump in the TA. I then ran the same tests using the same sample water I used for the new chemical readings.
A 7183 is a lipophilic prodrug of aciclovir that was under preclinical development with Drug Innovation and Design in the USA for the topical treatment of
Arete Therapeutics Presents Positive Clinical and Preclinical Data for AR9281 - read this article along with other careers information, tips and advice on BioSpace
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
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 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?
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?
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.
Cytotoxicity tests for high-throughput drug discovery.: Despite theoretical obstacles associated with performing cell-based assays in high-density formats (micr
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 ...
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.
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
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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
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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...
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 ...
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 ...
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 ...
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. ...
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Creative Animodel provides custom preclinical animal services for human hematopoiesis from model development, lead drug candidate efficacy studies, to toxicology testing.
In vitro testing includes both cell-based and cell-free systems that can be used to detect toxicity induced by xenobiotics. In vitro methods are especially useful in rapidly gathering intelligence regarding the toxicity of compounds for which none is available such as new chemical entities developed in the pharmaceutical industry. In addition to this, in vitro investigations are invaluable in providing information concerning mechanisms of toxicity of xenobiotics. This type of toxicity testing has gained popularity among the research and development community because of a number of advantages such as scalability to high throughput screening, cost-effectiveness and predictive power. Hepatotoxicity is one of the major causes of drug attrition and the high cost associated with drug development poses a heavy burden on the development of new chemical entities. Early detection of hepatotoxic agents by in vitro methods will improve lead optimisation and decrease the cost of drug development and reduce ...
About Neuralstem. Neuralstems patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for multiple central nervous system (CNS) diseases and conditions.. Neuralstems technology enables the discovery of small molecule compounds by systematic screening of chemical compounds against its proprietary human hippocampal stem cell line. The screening process has led to the discovery and patenting of molecules that Neuralstem believes may stimulate the brains capacity to generate new neurons, potentially reversing pathophysiologies associated with certain central and peripheral nervous system conditions.. The company has completed Phase 1a and 1b studies evaluating NSI-189, a novel neurogenic small molecule product candidate, for the treatment of major depressive disorder or MDD, and is currently conducting a Phase 2 efficacy study for MDD.. Neuralstems stem cell therapy product candidate, ...
One of the fundamental factors determining the success of a new drug candidate is the identification of a dose range that is both efficacious and safe. This is achieved via the use of pharmacokinetic (PK) and pharmacodynamic (PD) data to establish dose-(concentration)-response relationships for the various drug effects. Modelling and simulation (M&S) techniques are now commonly used to analyse clinical PKPD data as part of a model-based drug development framework, however, their use in the pre-clinical stages is limited and within the safety sciences is virtually non-existent. Application of such techniques to pre-clinical safety pharmacology data may help to improve the predictability of adverse effects compared to conventional methods. The aim of this project is to develop PKPD models using safety pharmacology data, which can be used to predict cardiovascular (CV) effects in man.Non-linear mixed effects modelling was used to analyse the PKPD relationships for the haemodynamic effects of ...
including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.. Nektars Cautionary Note Regarding Forward-Looking Statements. This press release contains forward-looking statements which can be identified by words such as: "will," "believe," "aim," "expect," "designed" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the therapeutic potential NKTR-214 in combination with entinostat, the enrollment of future clinical trials, and outcomes from clinical and preclinical studies of our new drug candidates. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans ...
A class of binding ligands for cocaine receptors and otherreceptors in the brain. Specifically, a novel family of compoundsshows high binding specificity and activity, and, in a radiolabeledform, can be used to bind to these receptors, for biochemicalassays and imaging techniques. Such imaging is useful fordetermining effective doses of new drug candidates in humanpopulations.
Recent insights into the pathophysiology of psoriasis have led to the identification of putative targets for pharmacological intervention. With the investigation for small molecule compounds that can...
Results Preclinical toxicology studies have shown RA Abs complete safety, the same was confirmed by absence of adverse effects or withdrawal in clinics. In a range of top-quality nonclinical studies RA Abs were shown to have antiviral activity against a wide spectrum of pathogens, even those the most dangerous (MERS-related coronavirus) or resistant to the existing therapy (Influenza A/H1N1/pdm09 Oseltamivir-resistant strain). Drugs efficacy was equal to that of the reference with similar total quality-of-life scores and no worsening in clinics. Moreover, in series of experiments of joint RA Abs use with the conventional drugs a capacity to increase their efficacy as well as toxicity decrease was demonstrated. RA Abs exert their MoA via change of target molecules conformation, reinforcement of receptor-ligand interaction as well as an increase in immune genes expression; thus mildly enhancing immune reactions without its exhaustion. ...
The humble laboratory mouse has taught us a phenomenal amount about embryonic development, disease, and evolution. And, for decades, the pharmaceutical industry has relied on these critters to test the safety and efficacy of new drug candidates. If it works in mice, so we thought, it should work in humans. But when it comes to…
The Laboratory for Molecular Modeling and Drug Design was established in March 2009, at the Faculty of Pharmacy of the Federal University of Goiás. Our research group is focused on designing of new drug candidates for infectious diseases such as Chagas disease, schistosomiasis, leishmaniasis, malaria and tuberculosis, as well as for cancer. Another important goal of our group is the development of predictive models for pharmacokinetics and toxicity properties. The work developed by our group has resulted in publications in international indexed journals, abstracts, dissertations and awards in national and international meetings of Medicinal and Computational Chemistry area. ...
By Helen Young Scientists at The Scripps Research Institute have developed a new drug candidate that lowers the growth rate of tumor cells in animal models1 in one of the most difficult cancers to battle: triple negative breast cancer. This is the first time that scientists have been able to take a genetic sequence and design […]. ...
By Helen Young Scientists at The Scripps Research Institute have developed a new drug candidate that lowers the growth rate of tumor cells in animal models1 in one of the most difficult cancers to battle: triple negative breast cancer. This is the first time that scientists have been able to take a genetic sequence and design […]. ...
EN) - High-throughput assay setup for the Investigator 24plex GO! Kit from Bode Buccal 2 Assembled Cassette samples using the STAR Q Punch ...
Computational and statistical methods development for high-throughput, high-content biological data. Modeling and integration of data from high throughput assays for biomarker discovery, clinical outcome prediction and disease classification.
Endothelial activation (endothelium - tissue that acts as a barrier between the blood stream and the surrounding tissues) with excessive recruitment and adhesion of immune cells plays a central role in the progression of sepsis. In this study the authors studied endothelial activation induced by plasma from highly septic patients and demonstrated the ability of polystyrene-divinylbenzene-based adsorbents (CytosSorb and Amberchrom) to reduce endothelial activation in a pore size-dependent manner. Specifically, in septic patients, blood was taken on admission to ICU, 1 hr and 24 hrs later. Primary monocytes were isolated and their purity and viability determined. Venous blood was also obtained from healthy volunteers. Blood from both sets of patients (normal and septic) was then diluted and passed through the adsorbers. Following this the blood was then passed over an endothelial layer. Results showed that treatment of stimulated whole blood with polystyrene-divinylbenzene-based cytokine ...
Ralph Garippa, Ph.D., independent consultant and former head of cell-based high-throughput screening (HTS) and microscopic imaging-based high-content
INTRODUCTION: Preclinical assessment of the heart rate corrected QT interval (QTc) is an important component of the cardiovascular safety evaluation in drug discovery. Here we aimed to quantify the translational relationship between QTc prolongation and shortening in the conscious telemetered dog and humans by a retrospective pharmacokinetic-pharmacodynamic (PKPD) analysis. METHODS: QTc effects of 2 proprietary compounds and 2 reference drugs (moxifloxacin and dofetilide) were quantified in conscious dogs and healthy volunteers via a linear and Emax pharmacokinetic-pharmacodynamic models. The translational relationship was quantified by correlating the QTc response from dog and human at matching free drug concentrations. RESULTS: A consistent translational relationship was found at low delta-QTc intervals indicating that a QTc change of 2.5-8 ms in dog would correspond to a 10 ms change in human. DISCUSSION: The translational relationship developed here can be used to predict the QTc liability ...
As a leading biotech company focusing exclusively on early drug discovery and development services, GenScript provides a comprehensive portfolio of services that include Bio-Reagent, Bio-Assay, Lead Optimization, and Antibody Drug Development.
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Designing a better molecule is just one aspect of computational research, but getting it synthesized for biological evaluation is the most significant component in a drug discovery program. A molecule
Our lab is particularly interested in identifying novel host machineries that regulate viral life cycle and contribute to viral pathogenesis, and further investigating the molecular mechanisms underlining their functions. To achieve this goal, we are developing and employing cutting-edge systematic approaches, including proteomic and functional genomic tools, to unbiasedly identify previously unappreciated host genes that regulate viral transcription, transition of latency and reactivation, and viral oncogenesis for HIV and herpesviruses. Novel host genes are further studied thoroughly in our lab using classic approaches of virology, cellular and molecular biology. The long-term goal of our lab is to comprehensively study host-virus relationships at multiple levels (genetically, biochemically, and serologically), as well as to improve these studies with more quantitative, dynamic and in vivo settings. Small-molecule compounds targeting key host machineries are also under development for ...
Director, Center for Drug Evaluation and Research, U.S. Food and Drug... Closing Discussion with Session Chairs, Panelists, and Audience Led by Workshop Chair. ...
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Clinical-stage oncology company Prescient Therapeutics Ltd (ASX:PTX; Prescient) announced that a pre-clinical study published in the scientific journa
In conclusion, there are many anti-aging strategies in development, some of which have shown considerable promise for slowing down aging or delaying the onset of age-related diseases. From multiple pre-clinical studies, it appears that upregulation of autophagy through autophagy enhancers, elimination of senescent cells using senolytics, transfusion of plasma from young blood, neurogenesis and BDN...
We offer comprehensive support in developing your hit compounds. Naturally such programs are realised most efficiently when biological actives originate from our screening collection. However, even if the hit compounds are from the collections of other vendors lead identification and optimization projects can proceed most productively in our hands. Sometimes for this we only need to synthesize first examples of the given chemical series and validate synthesis route.. ...
Whereas transgenic and viral overexpression of HGF in rodent β-cells markedly improves β-cell proliferation, survival, and function in three different in vivo rodent models (3-6), a necessary intermediate step toward bringing HGF to human clinical use is demonstrating efficacy in a species higher in the phylogenetic tree than rodents. Here, we demonstrate for the first time that HGF improves the quantity of engrafted β-cells as well as their function in the highest preclinical species, the NHP. These studies are significant, for they demonstrate that the efficacy of HGF clearly merits further study as a therapeutic agent for expanding β-cell mass and function in humans with diabetes.. In some senses, the results observed might have been anticipated, based on the efficacy of HGF in rat and mouse islets. On the other hand, there were three major unanticipated surprises in the current studies. First, HGF has been shown to drive replication in mouse, rat, as well as fetal, neonatal, and adult ...
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Many early-stage biotech companies face a significant funding gap when trying to develop a new drug from preclinical development to a proof of concept clinical trial. This funding gap is sometimes referred to as the "valley ...