Design and development of a series of borocycles as selective, covalent kallikrein 5 inhibitors.
Bioorg Med Chem Lett
; 29(20): 126675, 2019 10 15.
Article
in En
| MEDLINE
| ID: mdl-31521475
ABSTRACT
The connection between Netherton syndrome and overactivation of epidermal/dermal proteases, particularly Kallikrein 5 (KLK5) has been well established and it is expected that a KLK5 inhibitor would improve the dermal barrier and also reduce the pain and itch that afflict Netherton syndrome patients. One of the challenges of covalent protease inhibitors has been achieving selectivity over closely related targets. In this paper we describe the use of structural insight to design and develop a selective and highly potent reversibly covalent KLK5 inhibitor from an initial weakly binding fragment.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Benzamidines
/
Kallikreins
/
Serine Proteinase Inhibitors
/
Netherton Syndrome
Language:
En
Journal:
Bioorg Med Chem Lett
Year:
2019
Type:
Article
Affiliation country:
United kingdom