Novel flufenamic acid analogues as inhibitors of androgen receptor mediated transcription.
The androgen receptor (AR), which mediates the signals of androgens, plays a crucial role in prostate-related diseases. Although widely used, currently marketed anti-androgenic drugs have significant side effects. Several studies have revealed that non-steroidal anti-inflammatory drugs, such as flufenamic acid, block AR transcriptional activity. Herein we describe the development of small molecule analogues of flufenamic acid that antagonize AR. This novel class of AR inhibitors binds to the hormone binding site, blocks AR transcription activity, and acts on AR target genes.
Féau
Clémentine
C
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Arnold
Leggy A
LA
Kosinski
Aaron
A
Zhu
Fangyi
F
Connelly
Michele
M
Guy
R Kiplin
RK
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal; D045744:Cell Line, Tumor; D005439:Flufenamic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011944:Receptors, Androgen / Q000378:metabolism; D013329:Structure-Activity Relationship; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D000099159:Tacrolimus Binding Protein 5
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D005439:Flufenamic Acid; D011944:Receptors, Androgen; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5