|
|||||
|
|
Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2) |
|
| Authors: | Methot Joey L Chakravarty Prasun K Chenard Melissa Close Joshua Cruz Jonathan C Dahlberg William K Fleming Judith Hamblett Christopher L Hamill Julie E Harrington Paul Harsch Andreas Heidebrecht Richard Hughes Bethany Jung Joon Kenific Candia M Kral Astrid M Meinke Peter T Middleton Richard E Ozerova Nicole Sloman David L Stanton Matthew G Szewczak Alexander A Tyagarajan Sriram Witter David J Secrist J Paul Miller Thomas A |
| Affiliation: | Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. joey_methot@merck.com |
| Abstract: | We report herein the initial exploration of novel selective HDAC1/HDAC2 inhibitors (SHI-1:2). Optimized SHI-1:2 structures exhibit enhanced intrinsic activity against HDAC1 and HDAC2, and are greater than 100-fold selective versus other HDACs, including HDAC3. Based on the SAR of these agents and our current understanding of the HDAC active site, we postulate that the SHI-1:2 extend the existing HDAC inhibitor pharmacophore to include an internal binding domain. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |