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PDBsum entry 4ot6
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Transferase/transferase inhibitor
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PDB id
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4ot6
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References listed in PDB file
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Key reference
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Title
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Structure-Based drug design of rn486, A potent and selective bruton'S tyrosine kinase (btk) inhibitor, For the treatment of rheumatoid arthritis.
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Authors
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Y.Lou,
X.Han,
A.Kuglstatter,
R.K.Kondru,
Z.K.Sweeney,
M.Soth,
J.Mcintosh,
R.Litman,
J.Suh,
B.Kocer,
D.Davis,
J.Park,
S.Frauchiger,
N.Dewdney,
H.Zecic,
J.P.Taygerly,
K.Sarma,
J.Hong,
R.J.Hill,
T.Gabriel,
D.M.Goldstein,
T.D.Owens.
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Ref.
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J Med Chem, 2015,
58,
512-516.
[DOI no: ]
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PubMed id
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Abstract
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Structure-based drug design was used to guide the optimization of a series of
selective BTK inhibitors as potential treatments for Rheumatoid arthritis.
Highlights include the introduction of a benzyl alcohol group and a fluorine
substitution, each of which resulted in over 10-fold increase in activity.
Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J.
Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced
preclinical characterization based on its favorable properties.
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