|
|||||
|
|
Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1) |
|
| Authors: | Wilson Kevin J Witter David J Grimm Jonathan B Siliphaivanh Phieng Otte Karin M Kral Astrid M Fleming Judith C Harsch Andreas Hamill Julie E Cruz Jonathan C Chenard Melissa Szewczak Alexander A Middleton Richard E Hughes Bethany L Dahlberg William K Secrist J Paul Miller Thomas A |
| Institution: | Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. kevin_wilson2@merck.com |
| 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. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |