• Computational studies designed to assess polypharmacology reiterate these conclusions. (mdpi.com)
  • My major goal is to develop and employ different computational approaches towards the rational design of drugs with selective polypharmacology towards guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs) to treat central nervous system diseases. (unc.edu)
  • Results indicated that our computational efforts to establish a compendium of computational predictors and devise an integrative chemocentric informatics approach to study polypharmacology in silico will eventually lead to useful and reliable tools aimed at identifying and enriching chemical libraries with compounds that have the desired activities for more than one molecular target of interest. (unc.edu)
  • The rampant increase of public bioactivity databases has fostered the development of computational chemogenomics methodologies to evaluate potential ligand-target interactions (polypharmacology) both in a qualitative and quantitative way. (biomedcentral.com)
  • Achenbach J, Tiikkainen P, Franke L, Proschak E (2011) Computational tools for polypharmacology and repurposing. (springer.com)
  • Behavior-Based Screening as an Approach to Polypharmacological Ligands, in Polypharmacology in Drug Discovery. (psychogenics.com)
  • The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. (nih.gov)
  • Polypharmacology is a new scientific area focused on discovery, development, and pharmacological study of Multiple Targeting Designed Ligands (MTDL) able to simultaneously modify the activities of several interacting pharmacological targets ( Hopkins, 2008 ). (frontiersin.org)
  • comparison of compound-induced profiles using high-content imaging or cancer cell line panels and web-based tools for polypharmacology prediction. (springer.com)
  • The Connectivity Map (CMap) is a database collecting gene-expression profiles of drug-treated human cancer cells, which has been widely used for investigation of polypharmacology and drug repurposing. (elsevier.com)
  • and the investigation of polypharmacology as a strategy to develop more effective antivirals with higher barriers to resistance. (harvard.edu)
  • This effort resulted in identification of one of the first reported kinase-selective chemical probes for ERK5 (JWG-071), a BET selective inhibitor with 1 μM BRD4 IC 50 (JWG-115), and additional inhibitors with rationally designed polypharmacology (JWG-047, JWG-069). (nih.gov)
  • Through a polypharmacology approach, we have developed small-molecule α-helix mimetics with isoxazole, pyrazole, and thiazole scaffolds that function as dual inhibitors of Mcl-1 and HDM2. (chim.it)
  • We've come up with one drug that hits multiple targets through 'rational polypharmacology,' and our approach represents a new concept we believe will have great success in suppressing tumors," said Ross L. Cagan, Ph.D., Professor and Associate Dean at Mount Sinai School of Medicine, and senior author on the study. (healthcanal.com)
  • I believe that, within the next five years, we'll see more drugs entering clinical trials that use rational polypharmacology as the basis of drug discovery. (healthcanal.com)
  • Supercomputing may play an important role in a radical change in the pharmaceutical industry by enabling investigations aimed at discovering polypharmacology, the ability of drugs to interact with multiple targets in the body, according to an article recently published in the journal Molecular Simulation by a team of researchers from the University of Tennessee, Knoxville. (tennessee.edu)
  • Polypharmacology is the design or use of pharmaceutical agents that act on multiple targets or disease pathways. (wikipedia.org)
  • Polypharmacology suggests that more effective drugs can be developed by specifically modulating multiple targets. (wikipedia.org)
  • The universe of pharmaceutical possibilities consisting of the protein targets and the small medicinal molecules that interact in the body is so enormous that experimentation is not a feasible means of exploring the drug discovery space and polypharmacology. (tennessee.edu)
  • Prediction of polypharmacology of known drugs and new molecules against selected multiple targets is highly useful for finding new therapeutic applications of existing drugs (drug repositioning) and for discovering multi-target drugs with improved therapeutic efficacies by collective regulations of primary therapeutic targets, compensatory signalling and drug resistance mechanisms. (eurekaselect.com)
  • abstract = 'Drugs frequently require interactions with multiple targets-via a process known as polypharmacology-to achieve their therapeutic actions. (ku.dk)
  • Polypharmacology, one drug with multiple targets, serves as a basis for drug repurposing. (elsevier.com)
  • We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. (elsevier.com)
  • The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology. (nih.gov)
  • Bayesian target prediction algorithms predict the probability of an interaction between a compound and a panel of targets, thus assessing compound polypharmacology qualitatively, whereas structure-activity relationship techniques are able to provide quantitative bioactivity predictions. (biomedcentral.com)
  • Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets. (springer.com)
  • This polypharmacology may be a function of the nonspecific activity by each curcuminoid analogue on different targets, but it may also be a function of other factors that will be discussed. (hindawi.com)
  • Approaches that utilize multi-targeting/polypharmacology have the most promise in treating EVD. (mdpi.com)
  • It's also a cost effective model and my prediction is there is going to be more emphasis on whole animal polypharmacology approaches in cancer drug research in the future. (healthcanal.com)
  • One compound with exemplary polypharmacology was found to promote axon growth in a rodent spinal cord injury model. (elsevier.com)
  • We propose an integrated drug discovery pipeline combining in silico target prediction and proteochemometric modelling (PCM) for the respective prediction of compound polypharmacology and potency/affinity. (biomedcentral.com)
  • Whereas ritanserin exhibited polypharmacology in NSCLC proteomes, this compound showed unexpected specificity for c-RAF in the SCLC subtype, with negligible activity against other kinases mediating mitogen-activated protein kinase signaling. (aspetjournals.org)
  • However, translation of the polypharmacology of a given compound to its antiangiogenic efficacy remains a major technical challenge. (biomedcentral.com)
  • Polypharmacology remains to be one of the major challenges in drug development, and it opens novel avenues to rationally design the next generation of more effective but less toxic therapeutic agents. (wikipedia.org)
  • The clinical activities of PLK inhibitor BI-2536 and JAK2-FLT3 inhibitor TG101348 have been attributed to this unexpected polypharmacology, indicating that dual-kinase/bromodomain activity may be advantageous in a therapeutic context. (nih.gov)
  • In most previous cases, the need for a polypharmacology to reach a therapeutic effect is discovered retrospectively. (frontiersin.org)
  • An in silico model for interpreting polypharmacology in drug-target networks. (semanticscholar.org)
  • Luciana Scotti and Marcus T. Scotti, "Editorial (Thematic Issue: Polypharmacology in Drug Discovery)", Current Pharmaceutical Design (2016) 22: 3071. (eurekaselect.com)
  • This leads to hypotheses exploring the vast utility of multiple members of the folate pathway for modulating cellular metabolism, and includes an appealing capacity for prokaryotic-specific polypharmacology for antimicrobial applications. (mdpi.com)
  • Most drugs exert their effects via multi-target interactions, as hypothesized by polypharmacology. (chemaxon.com)
  • An examination of this agent's polypharmacology via in vitro and in situ phosphoproteomic profiling demonstrated an activity profile enriched for mediators involved in DNA damage repair. (aacrjournals.org)
  • In this study, we integrated the next-generation L1000-based CMap and an analytic Web tool, the L1000FWD, for systematic analyses of polypharmacology and drug repurposing. (elsevier.com)
  • To clarify the possible compatibility mechanism of formulae with systems polypharmacology analyses, we use Sini Decoction (SNT), which has been proven to be effective in treating cardiovascular diseases (CVD), as a model. (pitt.edu)
  • This study investigates the structural basis of polypharmacology at canonical GPCRs and illustrates how understanding characteristic patterns of ligand-receptor interaction and activation may ultimately facilitate drug design at multiple GPCRs. (ku.dk)
  • X. Liu, F. Zhu, X. H. Ma, Z. Shi, S. Y. Yang, Y. Q. Wei and Y. Z. Chen, "Predicting Targeted Polypharmacology for Drug Repositioning and Multi- Target Drug Discovery", Current Medicinal Chemistry (2013) 20: 1646. (eurekaselect.com)
  • Cyclica provides the pharmaceutical industry with an integrated and end-to-end enabling drug discovery platform focused on polypharmacology. (businesswire.com)
  • This appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development, efficacy and toxicity. (springer.com)
  • As we wrote in the discussion section of this paper, "our findings may provide evidence that cancer drug polypharmacology is a common MOA for reportedly target-specific compounds. (sciencemag.org)
  • Large-scale databases have been accumulated in recent years, and utilization and integration of these databases would be highly helpful for polypharmacology and drug repurposing. (elsevier.com)
  • 14] Since then, Polypharmacology has become a new branch of Pharmacology discipline and research field as well as one of the new direction and strategies for drug development. (wikipedia.org)
  • Curcumin polypharmacology plotted to show a rendered influence on p65-p50 transactivation potential showing a relatively more selective outcome if NF-kB is selected as the ultimate target of the polypharmacology. (hindawi.com)