ONO-8430506 是一种有效的，具有口服活性的 autotaxin (ATX)/ENPP2 抑制剂，抑制小鼠血浆中 ATX 活性，IC₉₀ 为 100 nM^[2]。

ONO-8430506 is an orally bioavailable and potent autotaxin (ATX)/ENPP2 inhibitor with the IC 90 of 100 nM for ATX activity in mouse plasma.

Solid

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is a secreted enzyme that has lysophospholipase D activity. The IC50s of ONO-8430506 for the ?lysophospholipase D (LysoPLD) activity of recombinant human ATX/ENPP2 are 5.1 nM in an assay using synthetic fluorescent substrate (FS-3) and 4.5 nM in an assay using a natural substrate (16:0-LPC).
ONO-8430506 shows efficient inhibition of lysophosphatidic acid (LPA) formation, with IC50s of approximately 10 nM with both recombinant and plasma derived ATX/ENPP2 from various animal species. has not independently confirmed the accuracy of these methods. They are for reference only.

ONO-8430506 (10 mg/kg/day; gavage; for 21 days) slows initial tumor growth and limits lung metastasis.
ONO-8430506 decreases the initial phase of breast tumor growth and subsequent 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.
ONO-8430506 (30 or 100 mg/kg) enhances the antitumor effect of Paclitaxel in a breast cancer model.
ONO-8430506 exhibits moderate oral bioavailability (rat 51.6%, dog 71.1%, and monkey 30.8%) and C max (rat 261, dog 1670, and monkey 63 ng/mL) following oral administration (rat 1, dog 1, and monkey 1 mg/kg).
ONO-8430506 exhibits terminal elimination half-lives (rat 3.4, dog 8.9, and monkey 7.9 h) due to low plasma clearance (8.2, 4.7, and 5.8 mL/min/kg respectively) combine

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

[1]. Matthew G K Benesch, et al. Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice. FASEB J. 2014 Jun;28(6):2655-66.
[2]. Hiroshi Saga, et al. A novel highly potent autotaxin/ENPP2 inhibitor produces prolonged decreases in plasma lysophosphatidic acid formation in vivo and regulates urethral tension. PLoS One. 2014 Apr 18;9(4):e93230.

In Vitro: DMSO : 100 mg/mL (216.67 mM; Need ultrasonic)配制储备液