ONO-8430506 is an orally available, potent autotaxin (ATX)/ENPP2 inhibitor (IC90: 100 nM) that inhibits ATX activity in mouse plasma.

ATX/ENPP2:100 nM

The IC50 values of ONO-8430506 against the lysophospholipase D (LysoPLD) activity of recombinant human ATX/ENPP2 are 5.1 nM and 4.5 nM, determined using synthetic fluorescent substrate (FS-3) and a natural substrate (16:0-LPC) assay, respectively.[2]
ONO-8430506 exhibits effective inhibition of lysophosphatidic acid (LPA) formation, demonstrating IC50 values of approximately 10 nM with both recombinant and plasma-derived ATX/ENPP2 derived from diverse animal species.[2]

ONO-8430506 (10 mg/kg/day; gavage; for 21 days) initially slows tumor growth and limits lung metastasis, with tumor size comparable to the vehicle group by day 13. It reduces the initial phase of breast tumor growth and lung metastases by ~60% in a syngeneic orthotopic mouse model. ONO-8430506 (oral; 30 mg/kg) demonstrates good pharmacokinetics and persistently inhibits plasma lysophosphatidic acid formation in rats. Additionally, ONO-8430506 (30 or 100 mg/kg) enhances the antitumor effect of Paclitaxel in a breast cancer model. The compound exhibits moderate oral bioavailability (rat 51.6%, dog 71.1%, monkey 30.8%) and Cmax (rat 261, dog 1670, monkey 63 ng/mL) following oral administration (rat 1, dog 1, and monkey 1 mg/kg).