NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease.

ABSTRACT:

Background and purpose

The K(Ca) 3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of K(Ca) 3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses.

Experimental approach

We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) with respect to potency and molecular site of action on K(Ca) 3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease (IBD).

Key results

NS6180 inhibited cloned human K(Ca) 3.1 channels (IC(50) = 9 nM) via T250 and V275, the same

SUBMITTER: Strobæk D 

PROVIDER: S-EPMC3572569 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature