ONO-8430506

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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 IC90 of 100 nM for ATX activity in mouse plasma.

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.

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 Cmax (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) combined with large volumes of distribution (1474, 1863, and 2275 mL/kg respectively) following intravenous administration (rat 0.3, dog 0.3, and monkey 0.3 mg/kg).Animal Model:Female BALB/c mice, 8-10 wk old (BALB/cAnNCrl) Dosage:10 mg/kg Administration:Gavaged daily for 21 days; 10 μL/g Result:Tumor growth in ONO-8430506-treated mice caught up to the vehicle group by day 13; thereafter, primary tumor size was not significantly different from the vehicle-treated mice. However, treatment with ONO-8430506 decreased the numbers of metastatic nodules in the lungs at day 21 by ~60%.

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Angiogenesis

PDE

PDE

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1354805-08-5

461.53

C27H28FN3O3

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 100 mg/mL (216.67 mM; 超声助溶 )

OC(=O)C12CCC(CC(=O)N3CCc4c(C3)n(Cc3ccc(F)cc3)c3ncccc43)(CC1)C2

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(-20℃)

With Ice Pack

≥ 2 years