5YJK

Human kallikrein 7 in complex with 1,4-diazepane-7-one 1-acetamide derivative

Summary for 5YJK

• Entry DOI: 10.2210/pdb5yjk/pdb
• Related: 5Y9L
• Descriptor: Kallikrein-7, (R)-2-(6-(5-chloro-2-methoxybenzyl)-3-(2,2-dimethylhydrazono)-7-oxo-1,4-diazepan-1-yl)-N-(3-(methylsulfonyl)phenyl)acetamide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: protease, inhibitor complex, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted : P49862
• Total number of polymer chains: 1
• Total formula weight: 25088.11

Authors

Sugawara, H. (deposition date: 2017-10-11, release date: 2017-12-06, Last modification date: 2024-10-09)

Primary citation

Murafuji, H.,Sakai, H.,Goto, M.,Imajo, S.,Sugawara, H.,Muto, T.
Discovery and structure-activity relationship study of 1,3,6-trisubstituted 1,4-diazepane-7-ones as novel human kallikrein 7 inhibitors
Bioorg. Med. Chem. Lett., 27:5272-5276, 2017

PubMed Abstract: Compound 1, composed of a 1,3,6-trisubstituted 1,4-diazepane-7-one, was discovered as a novel human kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme, SCCE) inhibitor, and its derivatives were synthesized and evaluated. Structure-activity relationship studies of the amidoxime unit and benzoic acid part of this new scaffold led to the identification of 25 and 34, which were more potent than the hit compound, 1. The X-ray co-crystal structure of compound 25 and human KLK7 revealed the characteristic interactions and enabled explanations of the structure-activity relationship.

PubMed: 29102227
DOI: 10.1016/j.bmcl.2017.10.030

Experimental method

X-RAY DIFFRACTION (2.4 Å)