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Owing to the intrinsic polypharmacological nature of most small-molecule kinase inhibitors, there is a need for computational models that enable systematic exploration of the chemogenomic landscape underlying druggable kinome toward more efficient kinome-profiling strategies. We implemented VirtualKinomeProfiler, an efficient computational platform that captures distinct representations of chemical similarity space of the druggable kinome for various drug discovery endeavors. By using the computational platform, we profiled approximately 37 million compound-kinase pairs and made predictions for 151,708 compounds in terms of their repositioning and lead molecule potential, against 248 kinases simultaneously. Experimental testing with biochemical assays validated 51 of the predicted interactions, identifying 19 small-molecule inhibitors of EGFR, HCK, FLT1, and MSK1 protein kinases. The prediction model led to a 1.5-fold increase in precision and 2.8-fold decrease in false-discovery rate, when compared with traditional single-dose biochemical screening, which demonstrates its potential to drastically expedite the kinome-specific drug discovery process.
This article was published in the following journal.
Name: Cell chemical biology
Chirality is important in drug discovery since stereoselective drugs can ameliorate therapeutic difficulties including adverse toxicity and poor pharmacokinetic profiles. The human kinome, a major dru...
The large-scale kinome-wide virtual profiling for small molecules is a daunting task by experimental and traditional in silico drug design approaches. Recent advances in deep learning algorithms have ...
Computer-Aided Drug Design has developed into a powerful suite of methods that complement experimental approaches to the identification of new pharmacologically active compounds. In particular, virtua...
Biological rhythmicity is fundamental to almost all organisms on Earth and plays a key role in health and disease. Identification of oscillating signals could lead to novel biological insights, yet it...
Drug repositioning, or the identification of new indications for approved therapeutic drugs, has gained substantial traction with both academics and pharmaceutical companies because it reduces the cos...
The purpose of this study is to determine whether repositioning frequency can be extended for nursing home (NH) residents who are low, moderate, and high risk for pressure ulcer (PrU) deve...
Evaluate appropriate performance of Electronic Repositioning™ (ER) in the clinical routine, cumulative incidence of phrenic nerve stimulation (PNS) & success rates of ER to remove it, v...
The purpose of this study is to determine whether personalized titanium plates can achieve better accuracy than CAD/CAM surgical splint in maxilla repositioning in orthognathic surgery, an...
Since the introduction of the lip repositioning procedure by a number of modifications to the technique have been introduced. All these modifications were made to prevent the main complica...
Comparison of treatment efficacy of a mechanical rotational chair (TRV-chair) vs. manual repositioning maneuvers in BPPV
Activation analysis in which the specimen is bombarded with neutrons. Identification is made by measuring the resulting radioisotopes. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENETIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with POLYMERASE CHAIN REACTION.
The identification, analysis, and resolution of moral problems that arise in the care of patients. (Bioethics Thesaurus)
Biochemical identification of mutational changes in a nucleotide sequence.
The field of information science concerned with the analysis and dissemination of data through the application of computers.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...