title: Synthesis and biological evaluation of novel human Pin1 inhibitors with benzophenone skeleton.
abstract: A series of novel benzophenone derivatives were prepared and their inhibitory activities were evaluated on hPin1. Of all the synthesized compounds, the most active compound displayed inhibitory activities with an IC(50) value of 5.99 μmol/L. Preliminary structure-activity relationships were analyzed in details and the binding mode of the titled compounds was predicted using FlexX algorithm. The results of this research will shed light on further design and optimization of novel small molecule Pin1 inhibitors.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
authors.forename: Decai
authors.initials: D
authors.lastname: Fu
authors.forename: Hongrui
authors.initials: H
authors.lastname: Song
authors.forename: Bailing
authors.initials: B
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001577:Benzophenones; D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011994:Recombinant Proteins; C047723:benzophenone; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase