• A cholesterol-tethered platinum ii-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity. (cetbwh.org)
  • Integration of a machine learning-derived signature of response with in vitro assessment of LP-184 efficacy facilitated the derivation of manageable yet robust biomarkers which can be used to predict drug sensitivity with high accuracy and clinical value. (biomedcentral.com)
  • Dopamine receptor occupancy using [ 11 C]-raclopride PET is familiar to neuroscientists when used 10 as a PD biomarker of antipsychotic drug efficacy. (drugtargetreview.com)
  • In rheumatology, change in the transfer constant K trans in dynamic contrast-enhanced MRI is used ( Panel 2 ) as a PD biomarker of drug efficacy in synovitis, in addition to its more familiar use in oncology. (drugtargetreview.com)
  • Evaluate the impact of target inhibitors and degraders on efficacy and safety-related translational biomarkers with our BioMAP phenotypic platform. (fimecs.com)
  • Understanding the causes of CRC would enable the rational development of preventative agents, biomarkers of risk and potentially new chemotherapy drugs. (ukri.org)
  • In fact, the opposite is true: imaging measurements (imaging biomarkers) are used daily in drug development and in personalised medicine. (drugtargetreview.com)
  • Indeed, imaging biomarkers were used by the FDA as surrogate endpoints for 30 separate drug approvals between 2010 and 2014 1 . (drugtargetreview.com)
  • Some imaging biomarkers are very familiar to drug developers. (drugtargetreview.com)
  • Imaging tests are increasingly used as pharmacodynamic (PD) and safety biomarkers in early drug development. (drugtargetreview.com)
  • In particular, transcriptional signatures of drug sensitivity may guide drug repositioning, prioritize drug combinations, and point to new therapeutic biomarkers. (biomedcentral.com)
  • Screening in vivo may be feasible, if a good starting point for Medicinal Chemistry and a clear strategy for differentiation exist. (docksci.com)
  • 2012). However, many drug discovery efforts rely on screening to identify starting points for Medicinal Chemistry, and screening in vivo in most cases is not commercially or ethically viable. (docksci.com)
  • Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity. (cetbwh.org)
  • Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. (dovepress.com)
  • SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. (dovepress.com)
  • Identify and characterize new, potent, and selective ligands that bind and reprogram E3 ligase substrate specificity with our E3scanTM ligand binding assays. (fimecs.com)
  • There, he has established a discovery chemistry group that focuses on developing first-in-class inhibitors for newly emerging biological targets, including resistant alleles of existing targets, as well as inhibitors of well-validated targets, such as Her3 and RAS, that have previously been considered recalcitrant to small molecule drug development. (stanford.edu)
  • Some Mek inhibitors showed promising antitumor activity, although schedules and doses associated with low systemic toxicity need to be defined. (biomedcentral.com)
  • Finally, several clinical trials are currently ongoing using MEK inhibitors in combination with chemotherapeutic drugs (including dacarbazine or paclitaxel). (biomedcentral.com)
  • A large number of potential drug targets have been cloned and functionally expressed, and enormous progress has been made in the development, miniaturization and automation of cell based assays on target molecules recombinantly expressed in mammalian cell lines. (docksci.com)
  • Through exploring the relations in between drug molecules and mouse ailment versions, our strategy was able to assess whether the corresponding model recapitulates the essential options of the human disorder. (hdac-inhibitors.com)
  • Dr. Gray's research has had broad impact in the areas of kinase inhibitor design and in circumventing drug resistance. (stanford.edu)
  • Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called 'gatekeeper' residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR. (stanford.edu)
  • Although the incidence of CRC has decreased, current treatments have serious side effects, with a recurrence rate of more than 50%, mainly due to resistance to conventional chemotherapy drugs[3, 4]. (researchsquare.com)
  • The long-term effectiveness of most antibiotic treatments is restricted by both pathogen drug resistance and non-target effects on the host's commensal microbial community. (nature.com)
  • Anti-infective drugs that do not perturb survival or viability of bacterial pathogens should be less likely to promote resistance than conventional antibiotics 1 , 2 . (nature.com)
  • Natural bioactive compounds derived from plant species show promising therapeutic properties to combat the emerging resistance in microbial pathogens, which can be exploited as next generation anti-infective drugs. (nature.com)
  • Curating drug CCRG pairs We searched the PubMed database that has a listing of essential phrases, this kind of as drug/compound/chemical/small molecule and sensitive/sensitivity/resistant/resistance/response within the title/abstract, and applying National Cancer Institute and gene/transcript/protein in any field from the literature. (hdac-inhibitors.com)
  • Development of a facile antibody-drug conjugate platform for increased stability and homogeneity. (cetbwh.org)
  • In 2021, Dr. Gray joined Stanford University where he has joined the Stanford Cancer Institute, Chem-H and the Innovative Medicines Accelerator (IMA) to spur the development of prototype drugs. (stanford.edu)
  • We then screened a patient-derived xenograft library to identify SCLC as a tumor type with enhanced sensitivity to calicheamicin ADCs. (aacrjournals.org)
  • Our pilot studies already suggest SHROOM2 (and related pathway components) is a drug target for developing cancer prevention agents. (ukri.org)
  • Our strategy starts with the calculation of drug-gene correlations and is followed by a pathway-oriented filtering and a network-diffusion analysis across the interactome. (biomedcentral.com)
  • Target based screening is likely to provide very good drug candidates for monogenic diseases, and the following collection of manuscripts is not meant to discourage the use of target based approaches. (docksci.com)
  • Here, target agnostic approaches using phenotypic assays may offer significant benefit. (docksci.com)
  • Viswanathan and colleagues reviewed the recent progress in the culture of hPSCs with emphasis on the importance of the environment surrounding these cells and high content analysis approaches for assay development. (docksci.com)
  • During his six year stay at GNF, Dr. Gray became the director of biological chemistry where he supervised a group of over fifty researchers integrating chemical, biological and pharmacological approaches towards the development of new experimental drugs. (stanford.edu)
  • The FDA and EMA want evidence that a new drug improves how the patients feels , functions, or survives , so almost anything else measured in a clinical trial is considered a biomarker. (drugtargetreview.com)
  • In toxicology, inhibition of liver organic anion transporters measured using dynamic gadoxetate-enhanced MRI provides a biomarker of risk of drug-induced liver injury ( Panel 3 ). (drugtargetreview.com)
  • When drug developers and regulatory authorities make decisions based on imaging biomarker data, they need to trust the validity of the tools they are using. (drugtargetreview.com)
  • Furthermore, an unfortunate association of factors such as tumor genetic complexity, overestimation of biomarker and drug potentials, as well as a poor understanding of tumor microenvironment in diagnosis and prognosis leads to the current levels of treatment failure regarding a vast majority of cancer types. (biomedcentral.com)
  • Since the advent of molecular cloning, target based screening has become the norm in pharmaceutical drug discovery. (docksci.com)
  • Most of these drugs interact relatively weakly with a number of targets, and the complete profile of their molecular interactions is not well-known. (docksci.com)
  • The perspective by Dr. Swinney analyzes the phenotypic end points used in the discovery of new molecular entities that have resulted from phenotypic drug discovery efforts. (docksci.com)
  • In this sense, the lack of technologies that would allow for molecular screening of individual stromal cell types poses a major challenge for the development of therapies targeting the tumor microenvironment. (biomedcentral.com)
  • The integration of large-scale drug sensitivity screens and genome-wide experiments is changing the field of pharmacogenomics, revealing molecular determinants of drug response without the need for previous knowledge about drug action. (biomedcentral.com)
  • Nathanael Gray is the Krishnan-Shah Family Professor of Chemical and Systems Biology at Stanford, Co-Director of Cancer Drug Discovery Co-Leader of the Cancer Therapeutics Research Program, Member of Chem-H, and Program Leader for Small Molecule Drug Discovery for the Innovative Medicines Accelerator (IMA). (stanford.edu)
  • Network biology strategies like module detection are able to digest the outcome of large-scale pharmacogenomic initiatives, thereby contributing to their interpretability and improving the characterization of the drugs screened. (biomedcentral.com)
  • issues that often frustrate the present target based drug discovery programs. (docksci.com)
  • In order to limit the reliance on non-predictive animal models, screening strategies utilizing human pluripotent stem cells (hPSCs) are increasingly considered as resources for drug discovery. (docksci.com)
  • In the early phases of drug discovery, phenotypic assays can be used to further our knowledge of the disease process and to identify those end points that are most likely to translate to the clinic. (docksci.com)
  • and discovery that sphingosine-1-phosphate receptor-1 (S1P1) is the pharmacologically relevant target of the immunosuppressant drug Fingomilod (FTY720) followed by the development of Siponimod (BAF312), which is currently used for the treatment of multiple sclerosis. (stanford.edu)
  • Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. (medsci.org)
  • However, available evidence indicates that CRC incidence can be substantially reduced by early detection and prevention using drugs and/or dietary components. (ukri.org)
  • Colorectal cancer (CRC) is a common cancer but incidence could be reduced by early detection or prevention with drugs and/or dietary constituents/additives. (ukri.org)
  • Enable sensitive quantitation of PROTAC-mediated degradation of targets using Enzyme Fragment Complementation (EFC)-based cellular biosensor cell lines which combine EFC detection technology with CRISPR genome editing in our SPRINTerâ„¢ Protein Turnover Biosensor Assays. (fimecs.com)
  • In oncology, mouse xenograft models, based on a patient's tumor cells, have been used to select between drugs (Wu et al. (docksci.com)
  • In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods. (medsci.org)
  • Chemotherapeutic drugs target cancer-specific characteristics, such as alterations in DNA repair, which has complicated roles in oncogenesis and tumor progression. (biomedcentral.com)
  • One strategy to increase cure rates is the identification of patient-specific drug responses in tissue models that mimic the interaction between patient cancer cells and tumor environment. (regenhu.com)
  • However, several hurdles need to be overcome before widespread implementation of hPSC-based assays. (docksci.com)
  • The largest cell panels available today are derived from cancerous tissues, since a crucial step towards personalized cancer medicine is the identification of transcriptional signatures that can guide drug prescription. (biomedcentral.com)
  • Computationally designed antibody-drug conjugates self-assembled via affinity ligands. (cetbwh.org)
  • In the past year, four antibody-drug conjugates (ADC) were approved, nearly doubling the marketed ADCs in oncology. (aacrjournals.org)
  • This approach has delivered many clinical candidates but relatively few new drugs. (docksci.com)
  • Drug developers sometimes think of imaging as an emerging discipline, full of esoteric technologies of marginal relevance to real-world clinical drug development. (drugtargetreview.com)
  • Figure 1: Six imaging modalities most likely to be encountered in clinical drug development. (drugtargetreview.com)
  • Open data on the gene expression of the NCI-60 cell lines, provides a unique opportunity to add another dimension to the preclinical development of such drugs by interrogating correlations with gene expression patterns. (biomedcentral.com)
  • In recent years an even wider array of imaging technologies has been transforming drug development. (drugtargetreview.com)
  • Progress in microenvironment genetic studies represents a formidable opportunity for the development of new selective drugs because stromal cells have lower mutation rates than malignant cells, and should prove to be good targets for therapy. (biomedcentral.com)
  • Although providing a rich account of disease biology, these studies have failed to yield better drug therapies, as causality and response to drug perturbations cannot be inferred directly from two-state (diseased vs. healthy) differential gene expression analysis [ 2 , 3 ]. (biomedcentral.com)
  • The limited throughput of phenotypic assays compared to most target-based assays necessitates smaller libraries that are optimized with regard to biological and chemical diversity. (docksci.com)
  • Earlier scientific studies have identified disease genes, radioresistance genes and drug target genes primarily based on Gene Ontology and protein interaction networks. (hdac-inhibitors.com)
  • Soon after doing these 4 methods, we eventually identified CRGs for every drug, as a result, researchers will likely be in a position to perform follow up research on unique drugs and genes of curiosity. (hdac-inhibitors.com)
  • The drug CCRG pairs had been derived from experimental scientific studies of NCI 60 cell lines, with the 492 retrieved published papers, 150 pairs of drug CCRG were documented, such as 64 medication and 94 genes. (hdac-inhibitors.com)
  • Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. (medsci.org)
  • Tomino Y. Long term effects of dilazep hydrochloride, an anti-platelet drug, on patients with IgA nephropathy-reports of 5-year treatment. (dnapk-signaling.com)
  • We apply our approach to 189 drugs tested in 671 cancer cell lines and observe a connection between gene expression levels of the modules and mechanisms of action of the drugs. (biomedcentral.com)
  • Provided that the panel of cell lines is large enough, this approach allows for a new type of gene expression analysis where basal expression levels are correlated to drug response phenotypes. (biomedcentral.com)
  • Edges with the network had been weighted by Pearsons correlation coefficient concerning gene expression and drug action. (hdac-inhibitors.com)
  • In Stage four we more refined the drug candidate CRG pair using the PLX4032 ic50 Pearsons correlation coef ficient between gene expression and drug exercise. (hdac-inhibitors.com)
  • Conclusions Within the current do the job, we launched a brand new cross species gene expression module comparison technique to produce quite possibly the most of animal expression information and analyze the effectiveness of animal models in drug analysis. (hdac-inhibitors.com)
  • Promising examples include anti-microbial assays, cell proliferation, platelet aggregation, and insulin release from pancreatic β-cells. (docksci.com)
  • Newly validated Arginase1 and IDO1 monoclonal antibodies add a functional readout of the immunosuppressive TME to phenotypic marker analysis. (labroots.com)
  • Another challenge involves the identification of a phenotypic end point associated with the disease of interest. (docksci.com)
  • Patients were subsequently treated with disease modifying antirheumatic drugs (usually methotrexate, sulphasalazine, or a combination of both). (exposed-skin-care.net)
  • discusses the potential for using zebrafish as a model system, enabling large scale behavior based screens for central nervous system disorders. (docksci.com)
  • The phenotypic transformation of proliferation and migration in vascular smooth muscle cells (VSMCs) from media to intima is the basic pathology of neointimal hyperplasia after angioplasty in hypertensive patients. (hindawi.com)
  • Register your specific details and specific drugs of interest and we will match the information you provide to articles from our extensive database and email PDF copies to you promptly. (dovepress.com)
  • Thus, we constructed an first drug candidate CRG network that incorporated two types of nodes, drug nodes, during which exercise information were obtainable, and gene nodes through which expression data had been obtainable in NCI 60 cell lines. (hdac-inhibitors.com)
  • In this case, phenotypic screening relies on an appropriate tissueor cell-based assay that can be miniaturized and used in combination with high throughput tools. (docksci.com)
  • Single-cell ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing, scATAC-seq) is a relatively new and powerful technique that allows researchers to identify open chromatin r. (labroots.com)
  • To simplify drug signatures, we have developed a network-based methodology to identify functionally coherent gene modules. (biomedcentral.com)
  • Although imaging studies create pictures, these are only useful to the drug developer when converted to a number or a score that can be used in significance testing or patient inclusion. (drugtargetreview.com)
  • In 2D culture, all cells can proliferate at a relatively constant rate in a planar space, and can be provided uniform access to nutrients, oxygen or drugs. (medsci.org)
  • The US Preventive Services Task Force (USPSTF) recommends against screening (with serum CA125 level or transvaginal ultrasonography) for ovarian cancer in the general population. (medscape.com)
  • Over the last decade, research on antimicrobials has shifted towards an alternative approach to combat pathogens using anti-infective drugs that selectively interrupt virulence pathways to help prevent or cure bacterial infections. (nature.com)
  • An understanding of the immune regulatory context of the TME is required to harness the power of the antitumor immune response. (labroots.com)