title: 1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of estrogen-related receptor α.
abstract: Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure-activity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2,3-triazoles as novel suppressors of ERRα transcriptional functions. The most promising compound, 2-aminophenyl-(1-(3-isopropylphenyl)-1H-1,2,3-triazol-4-yl)methanone (14n), potently suppressed the transcriptional functions of ERRα with IC50 = 0.021 μM in a cell-based reporter gene assay and also decreased both the mRNA levels and the protein levels of ERRα and the downstream targets. This compound inhibited the proliferation and migration of breast cancer cells with high level of ERRα. Preliminary pharmacokinetic studies suggested that it possessed a good pharmacokinetic profile with an oral bioavailability of 71.8%. The compounds may serve as novel small molecule probes for further validation of ERRα as a molecular target for anticancer drug development.
authors: Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou 510530, China.
authors: Shilin
authors: S
authors: Xu
authors: Xiaoxi
authors: X
authors: Zhuang
authors: Xiaofen
authors: X
authors: Pan
authors: Zhang
authors: Z
authors: Zhang
authors: Lei
authors: L
authors: Duan
authors: Yingxue
authors: Y
authors: Liu
authors: Lianwen
authors: L
authors: Zhang
authors: Xiaomei
authors: X
authors: Ren
authors: Ke
authors: K
authors: Ding
mesh_terms: D000284:Administration, Oral; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D001943:Breast Neoplasms; D002460:Cell Line; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D008156:Luciferases; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014230:Triazoles; D000097983:ERRalpha Estrogen-Related Receptor; C582925:2-aminophenyl-(1-(3-isopropylphenyl)-1H-1,2,3-triazol-4-yl)methanone