title: In vitro inhibition of AKR1Cs by sulphonylureas and the structural basis.
abstract: Recent epidemiological studies show conflicting data for the first-line anti-diabetic sulphonylureas drugs in treating cancer progression in type II diabetes patients. How sulphonylureas promote or diminish tumor growth is not fully understood. Here, we report that seven sulphonylureas exhibit different in vitro inhibition towards AKR1Cs (AKR1C1, AKR1C2, AKR1C3), which are critical steroid hormone metabolism enzymes that are related to prostate cancer, breast cancer and endometrial diseases. Interactions of the sulphonylureas and AKR1Cs were analyzed by X-ray crystallography.
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhai
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Kaixin
authors.initials: K
authors.lastname: Zeng
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China. Electronic address: liqing66@mail.sysu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Biopolcore, Inc., Baltimore, MD 21221, USA. Electronic address: xhu001@gmail.com.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
mesh_terms: D015089:20-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001665:Binding Sites; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D015089:20-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D006911:Hydroxyprostaglandin Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; D013453:Sulfonylurea Compounds; C115140:3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C487341:AKR1C3 protein, human
keywords: AKR1Cs; Crystal structures; Inhibition; Selectivity; Sulphonylureas