title: Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors.
abstract: We describe a series of potent and selective inhibitors of ADAM12 that were discovered using computational screening of a focused virtual library. The initial structure-based virtual screening selected 64 compounds from a 3D database of 67,062 molecules. Being evaluated by a cell-based ADAM12 activity assay, compounds 5, 11, 14, 16 were further identified as the potent and selective inhibitors of ADAM12 with low nanomolar IC50 values. The mechanism underlying the potency and selectivity of a representative compound, 5, was investigated through molecular docking studies.
authors.affiliation: Department of Life Science and National Research Laboratory of Proteolysis, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Myungsok
authors.initials: M
authors.lastname: Oh
authors.forename: Isak
authors.initials: I
authors.lastname: Im
authors.forename: Yong Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jeong Hyeok
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hye Gyeong
authors.initials: HG
authors.lastname: Park
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
mesh_terms: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D017076:Computer-Aided Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D008565:Membrane Proteins; D011480:Protease Inhibitors; D051722:ADAM Proteins; D000072199:ADAM12 Protein; D008666:Metalloendopeptidases