Document Report Card
Basic Information
ID: ALA3407351
Journal: Eur J Med Chem
Title: Pyrido-imidazodiazepinones as a new class of reversible inhibitors of human kallikrein 7.
Authors: Arama DP, Soualmia F, Lisowski V, Longevial JF, Bosc E, Maillard LT, Martinez J, Masurier N, El Amri C.
Abstract: The human tissue kallikrein-7 (KLK7) is a chymotryptic serine protease member of tissue kallikrein family. KLK7 is involved in skin homeostasis and inflammation. Excess of KLK7 activity is also associated with tumor metastasis processes, especially in ovarian carcinomas, prostatic and pancreatic cancers. Development of Kallikrein 7 inhibitors is thus of great interest in oncology but also for treating skin diseases. Most of the developed synthetic inhibitors present several drawbacks such as poor selectivity and unsuitable physico-chemical properties for in vivo use. Recently, we described a practical sequence for the synthesis of imidazopyridine-fused [1,3]-diazepines. Here, we report the identification of pyrido-imidazodiazepinone core as a new potential scaffold to develop selective and competitive inhibitors of kallikrein-related peptidase 7. Structure-activity relationships (SAR), inhibition mechanisms and selectivity as well as cytotoxicity against selected cancer cell lines were investigated.
CiteXplore: 25682203