2. Academic Validation
  3. Design and synthesis of androgen receptor antagonists with bulky side chains for overcoming antiandrogen resistance

Design and synthesis of androgen receptor antagonists with bulky side chains for overcoming antiandrogen resistance

  • J Med Chem. 2009 Sep 10;52(17):5546-50. doi: 10.1021/jm801218k.
Jinming Zhou 1,  Guoyan Geng,  Qingwen Shi,  Francoise Sauriol,  Jian Hui Wu
Affiliations

Affiliation

  • 1 Montreal Centre for Experimental Therapeutics in Cancer, Segal Cancer Center, McGill University, Montreal, Quebec, Canada.
PMID: 19725582 DOI: 10.1021/jm801218k
Abstract

Incorporation of curcumin and beta-ionone into one chemical entity led to identification of a novel antiandrogen with two bulky side chains, 6, which is a pure antagonist of the wild-type and the T877A, W741C, and H874Y mutated androgen receptors (AR), showing no cross-reactivity with Progesterone Receptor and low micromolar cytotoxicity in LNCaP, PCa-2b, 22Rv1, and C4-2B prostate Cancer cells. Molecular modeling indicates 6 adopts a "Y"-shape conformation and forms multiple hydrogen bonds with AR backbone.

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