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Fragment based discovery of a novel and selective PI3 kinase inhibitor.

Abstract：

:We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed into potent and ligand efficient lead compounds using structure guided fragment growing and merging strategies. This led to a potent, selective, and cell permeable PI3γ kinase inhibitor with good metabolic stability that was useful as a preclinical tool compound.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Hughes SJ,Millan DS,Kilty IC,Lewthwaite RA,Mathias JP,O'Reilly MA,Pannifer A,Phelan A,Stühmeier F,Baldock DA,Brown DG

doi

10.1016/j.bmcl.2011.07.117

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

6586-90

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01063-8

journal_volume

21

pub_type

杂志文章

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