ATX inhibitor 26 is an Autotaxin (ATX) inhibitor with an IC50 of 57 nM in human plasma. It effectively inhibits cell migration and collagen gel contraction. Additionally, ATX inhibitor 26 demonstrates significant antifibrotic activity, reducing collagen deposition in a Bleomycin (BLM)-induced pulmonary fibrosis model.

ATX:57 nM

ATX inhibitor 26 (Compound 27a) (500 nM) demonstrates excellent inhibitory activity in human plasma, achieving an ATX inhibition rate of 94.1% with an IC50 of 39.2 nM and surpassing 90% inhibition of lysophospholipase D (LysoPLD) with an IC50 of 57.2 nM. At 3.0 μM, over 12 to 48 hours, it significantly inhibits LPC/TGF-β-induced MAPK activation in L132, A549, and WI38 cells. Additionally, ATX inhibitor 26, in the range of 0-6.0 μM for 0.5-6.0 hours, modulates MAPK signaling in L132 cells in a dose- and time-dependent manner, reducing phosphorylation levels of ERK, p38, and JNK within 30 minutes at concentrations of ≥0.5 μM. At 3.0 μM for 0-48 hours, it markedly decreases both basal and TGF-β-induced A549 cell migration and WI38 cell collagen gel contraction.

ATX inhibitor 26 (Compound 27a), administered orally at a dose of 1 or 2 mg/kg once daily for 21 days, reduces collagen deposition and expression levels of LPAR1 and p-ERK1/2 in a BLM-induced pulmonary fibrosis model. It also lowers the mRNA levels of α-SMA, Col1A1, and pro-inflammatory markers IL-6, IL-1β, and INF-γ.