Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2014 Dec 15;24(24):5683-5687. doi: 10.1016/j.bmcl.2014.10.067. Epub 2014 Oct 27.

Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase.

Author information

1
Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
2
WuXi AppTec Co., Ltd, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, PR China.

Abstract

A series of 3,6-disubstituted dihydropyrones were identified as inhibitors of human lactate dehydrogenase (LDH)-A. Structure activity relationships were explored and a series of 6,6-spiro analogs led to improvements in LDHA potency (IC50 <350 nM). An X-ray crystal structure of an improved compound bound to human LDHA was obtained and it illustrated additional opportunities to enhance the potency of these compounds, resulting in the identification of 51 (IC50=30 nM).

KEYWORDS:

LDHA; Tumor metabolism; X-ray crystal structure

PMID:
25467161
DOI:
10.1016/j.bmcl.2014.10.067
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center