Abstract
To overcome resistance to conventional anti-androgens of human androgen receptor (AR), the allosteric site of the AR binding function 3 (BF3) was investigated as an alternative target for small molecule therapeutics. A library of 1H-indole-2-carboxamides were discovered as BF3 inhibitors and exhibited strong antiproliferative activity against LNCaP and enzalutamide-resistant prostate cancer cell lines. Several of the lead compounds may prove of particular benefit as a novel alternative treatment for castration-resistant prostate cancers.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Allosteric Site
-
Amides / chemical synthesis
-
Amides / chemistry*
-
Amides / pharmacology
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Drug Resistance, Neoplasm
-
Drug Screening Assays, Antitumor
-
Humans
-
Indoles / chemical synthesis
-
Indoles / chemistry*
-
Indoles / pharmacology
-
Male
-
Models, Molecular
-
Prostatic Neoplasms, Castration-Resistant / drug therapy
-
Receptors, Androgen / metabolism*
-
Small Molecule Libraries / chemistry
-
Structure-Activity Relationship
Substances
-
Amides
-
Antineoplastic Agents
-
Indoles
-
Receptors, Androgen
-
Small Molecule Libraries