6AHS

Mouse Kallikrein 7 in complex with imidazolinylindole derivative

Summary for 6AHS

• Entry DOI: 10.2210/pdb6ahs/pdb
• Descriptor: Kallikrein-7, 1-[(2-chlorophenyl)sulfonyl]-5-methyl-3-[(4R)-2-methyl-4,5-dihydro-1H-imidazol-4-yl]-1H-indole, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: protease, hydrolase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 25218.27

Authors

Sugawara, H. (deposition date: 2018-08-20, release date: 2019-01-02, Last modification date: 2024-11-20)

Primary citation

Murafuji, H.,Muto, T.,Goto, M.,Imajo, S.,Sugawara, H.,Oyama, Y.,Minamitsuji, Y.,Miyazaki, S.,Murai, K.,Fujioka, H.
Discovery and structure-activity relationship of imidazolinylindole derivatives as kallikrein 7 inhibitors.
Bioorg. Med. Chem. Lett., 29:334-338, 2019

PubMed Abstract: A series of imidazolinylindole derivatives were discovered as novel kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme) inhibitors. Structure-activity relationship (SAR) studies led to the identification of potent human KLK7 inhibitors. By further modification of the benzenesulfonyl moiety to overcome species differences in inhibitory activity, potent inhibitors against both human and mouse KLK7 were identified. Furthermore, the complex structure of 25 with mouse KLK7 could explain the SAR and the cause of the species differences in inhibitory activity.

PubMed: 30522951
DOI: 10.1016/j.bmcl.2018.11.011

Experimental method

X-RAY DIFFRACTION (1.75 Å)