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PDBsum entry 6acr
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Signaling protein
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PDB id
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6acr
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References listed in PDB file
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Key reference
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Title
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Bis-Heteroaryl pyrazoles: identification of orally bioavailable inhibitors of activin receptor-Like kinase-2 (r206h).
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Authors
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K.Sekimata,
T.Sato,
N.Sakai,
H.Watanabe,
C.Mishima-Tsumagari,
T.Taguri,
T.Matsumoto,
Y.Fujii,
N.Handa,
T.Honma,
A.Tanaka,
M.Shirouzu,
S.Yokoyama,
K.Miyazono,
Y.Hashizume,
H.Koyama.
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Ref.
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Chem Pharm Bull (Tokyo), 2019,
67,
224-235.
[DOI no: ]
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PubMed id
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Abstract
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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.
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