title: Discovery of novel indole derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase.
abstract: A series of novel indole derivatives was designed and synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). The most potent compound 14c was identified with an IC50 value of 0.10 μM by testing the inhibitory activity against recombinant human FBPase. The structure-activity relationships were investigated on the substitution at 4- and 5-position of the indole scaffold. The binding interactions of the title compounds at AMP binding site of FBPase were predicted using CDOCKER algorithm.
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences＆Peking Union Medical College, Beijing 100050, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Bie
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences＆Peking Union Medical College, Beijing 100050, China.
authors.forename: Shuainan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences＆Peking Union Medical College, Beijing 100050, China.
authors.forename: Zhanmei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences＆Peking Union Medical College, Beijing 100050, China.
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences＆Peking Union Medical College, Beijing 100050, China. Electronic address: xubl@imm.ac.cn.
authors.forename: Bailing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences＆Peking Union Medical College, Beijing 100050, China. Electronic address: shenzhf@imm.ac.cn.
authors.forename: Zhufang
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D006597:Fructose-Bisphosphatase
keywords: Allosteric inhibitor; Diabetes; Fructose-1,6-bisphosphatase inhibitor; Indole derivative