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Virtual screening and biochemical evaluation to identify new inhibitors of mammalian target of rapamycin (mTOR).

Abstract：

:Mammalian target of rapamycin (mTOR) is a promising target for the development of anticancer medicines. Here, we report the first example for a successful application of the structure-based virtual screening to identify new mTOR inhibitors. Using the scoring function improved by implementing the ligand solvation effects on protein-ligand association, six novel mTOR inhibitors are found with IC50 values ranging from 8 to 60 μM. Because these new inhibitors are also computationally screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further development by structure-activity relationship studies to optimize the inhibitory and anticancer activities. Structural features relevant to the stabilization of the inhibitors in the ATP-binding site of mTOR are addressed in detail.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Park H,Choe H,Hong S

doi

10.1016/j.bmcl.2013.12.081

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

835-8

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)01465-0

journal_volume

24

pub_type

杂志文章

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