PAT-048 is a potent, selective and orally active autotaxin inhibitor, inhibits IL-6 mRNA expression, but shows no effect on autotaxin protein and pulmonary lysophosphatidic acid (LPA) production in lung fibrosis model. PAT-048 shows an IC50 and IC90 of 20 nM and 200 nM for autotaxin in mouse plasma. PAT-048 reduces dermal fibrosis in vivo[1][2]. IC50: 20 nM (Autotaxin, in mouse plasma)[1] IC90: 200 nM (Autotaxin, in mouse plasma)[1]
[1]. Castelino FV, et al. An Autotaxin/Lysophosphatidic Acid/Interleukin-6 Amplification Loop Drives Scleroderma Fibrosis. Arthritis Rheumatol. 2016 Dec;68(12):2964-2974. [2]. Black KE, et al. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. FASEB J. 2016 Jun;30(6):2435-50.