Anti-androgens with full antagonistic activity toward human prostate tumor LNCaP cells with mutated androgen receptor

Toshiyasu Ishioka; Aya Tanatani; Kazuo Nagasawa; Yuichi Hashimoto

doi:10.1016/s0960-894x(03)00575-4

Anti-androgens with full antagonistic activity toward human prostate tumor LNCaP cells with mutated androgen receptor

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2655-8. doi: 10.1016/s0960-894x(03)00575-4.

Authors

Toshiyasu Ishioka¹, Aya Tanatani, Kazuo Nagasawa, Yuichi Hashimoto

Affiliation

¹ Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

PMID: 12873487
DOI: 10.1016/s0960-894x(03)00575-4

Abstract

Anti-androgens were designed based on the principle of inhibiting the folding of helix 12 of the nuclear androgen receptor. The prepared anti-androgens exhibited full antagonistic activity toward human prostate tumor LNCaP cells with T877A point-mutated nuclear androgen receptor, as far as examined, towards which other known anti-androgens, including hydroxyflutamide, are inactive or act as androgen agonists.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Androgen Antagonists / chemical synthesis*
Androgen Antagonists / pharmacology
Binding, Competitive
Drug Design
Humans
Isoxazoles / chemical synthesis
Isoxazoles / pharmacology
Male
Molecular Structure
Point Mutation
Prostate-Specific Antigen / analysis
Protein Folding
Receptors, Androgen / biosynthesis
Receptors, Androgen / drug effects*
Receptors, Androgen / genetics
Testosterone
Tumor Cells, Cultured

Substances

Androgen Antagonists
Isoxazoles
Receptors, Androgen
Testosterone
Prostate-Specific Antigen