BioCentury
ARTICLE | Distillery Therapeutics

Autoimmune disease; inflammation

October 3, 2018 11:25 PM UTC

In vitro, mouse, rat and dog studies identified an aminotriazine-based Btk inhibitor that could help treat RA and allergy. Chemical synthesis, in vitro testing in activity assays and optimization of a series of previously reported pyrimidine analogs yielded an aminotriazine-based compound that inhibited activated and unactivated conformations of Btk with IC50 values of 4.2 and 0.39 nM, respectively. In a mouse model of RA, the compound decreased paw swelling and joint inflammation compared with vehicle. In a mouse model of type I allergy, the compound decreased plasma extravasation, a marker of inflammation. In mice, rats and dogs, the compound had 65%, 44% and 43% oral bioavailability, respectively. Next steps by Carna Biosciences Inc. could include testing the compound in additional animal models of RA and allergy.

AbbVie Inc. and Johnson & Johnson market Imbruvica ibrutinib, a covalent Btk inhibitor, for multiple lymphomas and leukemias and graft-versus-host disease (GvHD), and have the compound in Phase I/II through Phase III testing for multiple other cancers...

BCIQ Company Profiles

Carna Biosciences Inc.

BCIQ Target Profiles

Bruton's tyrosine kinase (Btk)