title: Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening.
abstract: A series of hK6 inhibitors with a para-amidobenzylamine P1 group and a 2-hydroxybenzamide scaffold linker was discovered through virtual screening. The X-ray structure of hK6 complexed with compound 9b was determined to a resolution of 1.68Å. The tertiary folding of the hK6 complexed with the inhibitor is conserved relative to the structure of the apo-protein, whereas the interaction between hK6 and the inhibitor is consistent with both the SAR and the in silico model used in the virtual screening.
authors.affiliation: Molecular Innovative Therapeutics, Sanofi Pharmaceuticals, Bridgewater, NJ, USA. guyan.liang@verizon.net
authors.forename: Guyan
authors.initials: G
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Aldous
authors.forename: Su-Fen
authors.initials: SF
authors.lastname: Pu
authors.forename: Shujaath
authors.initials: S
authors.lastname: Mehdi
authors.forename: Elaine
authors.initials: E
authors.lastname: Powers
authors.forename: Tianhui
authors.initials: T
authors.lastname: Xia
authors.forename: Rachel
authors.initials: R
authors.lastname: Wang
mesh_terms: D001549:Benzamides / Q000737:chemistry*; D001596:Benzylamines / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C524082:2-hydroxybenzamide; D001549:Benzamides; D001596:Benzylamines; D015842:Serine Proteinase Inhibitors; C103551:KLK6 protein, human; D007610:Kallikreins