title: Identification of benzothiophene amides as potent inhibitors of human nicotinamide phosphoribosyltransferase.
abstract: Nicotinamide phosphoribosyltransferase (Nampt) is an attractive therapeutic target for cancer. A Nampt inhibitor with novel benzothiophene scaffold was discovered by high throughput screening. Herein the structure-activity relationship of the benzothiophene Nampt inhibitor was investigated. Several new inhibitors demonstrated potent activity in both biochemical and cell-based assays. In particular, compound 16b showed good Nampt inhibitory activity (IC50=0.17 μM) and in vitro antitumor activity (IC50=3.9 μM, HepG2 cancer cell line). Further investigation indicated that compound 16b could efficiently induce cancer cell apoptosis. Our findings provided a good starting point for the discovery of novel antitumor agents.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: He
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Tianying
authors.initials: T
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: cymiao@smmu.edu.cn.
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Miao
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: shengcq@hotmail.com.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D054409:Nicotinamide Phosphoribosyltransferase
keywords: Antiproliferative activity; Nampt inhibitors; Structure–activity relationship