Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors.
Tools
Tools
Whitehead, Lewis, Vash, Brian, Dobler, Markus, Radetich, Branko, Grob, Jonathan, Mcriner, Andrew, Pancost, Margaret, Patnaik, Anup, Shao, Wenlin, Shultz, Michael, Tichkule, Ritesh, Tommasi, Ruben, Zhu, Yanyi, Wang, Ping, Atadja, Peter, Stams, Travis and Claiborne, Tavina (2011) Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors. Bioorganic and Medicinal Chemistry.
Abstract
Herein we report the discovery of a family of simple, amino acid derived class I HDAC inhibitors. By means of traditional medicinal chemistry optimization methods in partnership with X-ray crystallography approaches and molecular modeling techniques, excellent HDAC8 selectivity was achieved. Isoform selectivity criteria is discussed on the basis of X-ray crystal structures of our novel inhibitors bound to HDAC8, marking the first reported exploitation of the HDAC acetate binding tunnel with a non-natural substrate conferring isoform selectivity.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Keywords: | Histone deacetylase, X-ray crystallography, Selectivity, acetate release hypothesis, metal binding. |
| Related URLs: | |
| Date Deposited: | 13 Oct 2015 13:16 |
| Last Modified: | 13 Oct 2015 13:16 |
| URI: | https://oak.novartis.com/id/eprint/1818 |