当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity.

Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity.

Abstract：

:The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. The iterative inhibitor design and evaluation with assistance of the selectivity screen served to differentiate otherwise indistinguishable inhibitors permitting the simultaneous optimization of potency and selectivity. Significantly, the simultaneous assessment of all potential competitive enzymes with the selectivity screen does not require the use of expressed or purified enzymes or a competitive substrate, no modification of the inhibitors is required, and the relative potency for competitive enzymes can be quantified (IC50's) including those that lack known substrates or function.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Leung D,Du W,Hardouin C,Cheng H,Hwang I,Cravatt BF,Boger DL

doi

10.1016/j.bmcl.2004.12.085

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

1423-8

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(05)00018-1

journal_volume

15

pub_type

杂志文章

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