Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1).

Abstract:

:An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (>100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and improved physical properties. Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog.

journal_name

Bioorg Med Chem Lett

authors

Wilson KJ,Witter DJ,Grimm JB,Siliphaivanh P,Otte KM,Kral AM,Fleming JC,Harsch A,Hamill JE,Cruz JC,Chenard M,Szewczak AA,Middleton RE,Hughes BL,Dahlberg WK,Secrist JP,Miller TA

doi

10.1016/j.bmcl.2008.02.012

subject

Has Abstract

pub_date

2008-03-15 00:00:00

pages

1859-63

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)00192-3

journal_volume

18

pub_type

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