Abstract:
:Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure-activity relationship studies assisted by X-ray crystallographic analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) with good aqueous solubility, liver microsomal stability, and oral bioavailability.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Sekimata K,Sato T,Sakai N,Watanabe H,Mishima-Tsumagari C,Taguri T,Matsumoto T,Fujii Y,Handa N,Honma T,Tanaka A,Shirouzu M,Yokoyama S,Miyazono K,Hashizume Y,Koyama Hdoi
10.1248/cpb.c18-00598subject
Has Abstractpub_date
2019-01-01 00:00:00pages
224-235issue
3eissn
0009-2363issn
1347-5223journal_volume
67pub_type
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