Thursday, May 14, 2020

A Fast and Clean BTK Inhibitor [@london_lab]

Ronen Gabizon, Nir London
J. Med. Chem. 2020
https://doi.org/10.1021/acs.jmedchem.0c00597

Bruton’s tyrosine kinase (BTK) is a major drug target for B-cell related malignancies; however, existing BTK inhibitors approved for cancer treatment have significant off-targets that limit their use for autoimmune and inflammatory diseases. Remibrutinib (LOU064) is a novel covalent BTK inhibitor that binds an inactive BTK conformation, which affords it unprecedented selectivity. Its optimization led to rapid BTK engagement in vivo and fast clearance, further limiting systemic exposure. Remibrutinib is currently in phase 2 clinical trials for treatment of chronic urticaria and Sjoegren’s syndrome.

Discovery of a Novel Serine-Targeting Covalent Inhibitor against HCES2A for Treating Drug-induced Diarrhea and Ulcerative Colitis

Danyang Hu, Hairong Zeng, Wenxuan Li, Ya Zhang, Xiaoqian Chi, Xiaoyu Liu, Haijing Zhang, Guangbo Ge, Xiaozhen Jiao, and Ping Xie Journal of ...