Virtual screening to successfully identify novel janus kinase 3 inhibitors: a sequential focused screening approach.
In an effort to identify novel Janus kinase 3 inhibitors, a sequential focused screening approach was adopted to search our in-house chemical database. By biologically testing only 79 selected compounds, we successfully identified 19 compounds showing IC 50 < 20 microM, with four of them in the nanomolar range. Particularly, a 3,5-disubstituted pyrazolo[4,3- d]pyrimidine scaffold emerged as a promising candidate for further lead optimization. With the advantages of efficiency and flexibility, this approach may be utilized to identify leads for other therapeutic targets.
Computer Assisted Drug Discovery, High-throughput Chemistry, and Inflammation Therapeutics, Research and Early Development, Johnson & Johnson Pharmaceutical Research and Development, LLC, Raritan, New Jersey 08869, USA. xin69chen@yahoo.com
Xin
X
Chen
Lawrence J
LJ
Wilson
Ravi
R
Malaviya
Rochelle L
RL
Argentieri
Shyh-Ming
SM
Yang
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D020128:Inhibitory Concentration 50; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D053616:Janus Kinase 3