当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).

Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).

Abstract：

:Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Moffett K,Konteatis Z,Nguyen D,Shetty R,Ludington J,Fujimoto T,Lee KJ,Chai X,Namboodiri H,Karpusas M,Dorsey B,Guarnieri F,Bukhtiyarova M,Springman E,Michelotti E

doi

10.1016/j.bmcl.2011.09.078

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

7155-65

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01322-9

journal_volume

21

pub_type

杂志文章

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