[CAS NO. 1354805-08-5] ONO-8430506
PRODUCTS SPECIFICATIONS [1354805-08-5]
DESCRIPTION [1354805-08-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 461.53 |
| Molecular Formula | C27H28FN3O3 |
| SMILES | O=C(C12CCC(CC1)(C2)CC(N3CC4=C(CC3)C5=C(N4CC6=CC=C(C=C6)F)N=CC=C5)=O)O |
Summary
In Vitro
Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is a secreted enzyme that has lysophospholipase D activity. The IC
50
s 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)
[2]
.
ONO-8430506 shows efficient inhibition of lysophosphatidic acid (LPA) formation, with IC
50
s of approximately 10 nM with both recombinant and plasma derived ATX/ENPP2 from various animal species
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ONO-8430506 (10 mg/kg/day; gavage; for 21 days) slows initial tumor growth and limits lung metastasis
[1]
.
ONO-8430506 decreases the initial phase of breast tumor growth and subsequent lung metastases by ~60% in a syngeneic orthotopic mouse model
[1]
.
ONO-8430506 (oral; 30 mg/kg) demonstrates good pharmacokinetics and persistently inhibits plasma lysophosphatidic acid formation in rats
[2]
.
ONO-8430506 (30 or 100 mg/kg) enhances the antitumor effect of Paclitaxel in a breast cancer model
[3]
.
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)
[3]
.
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)
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female BALB/c mice, 8-10 wk old (BALB/cAnNCrl) [1] |
| 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%. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
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)
Solvent & Solubility
DMSO : 100 mg/mL ( 216.67 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1667 mL | 10.8335 mL | 21.6671 mL |
| 5 mM | 0.4333 mL | 2.1667 mL | 4.3334 mL |
| 10 mM | 0.2167 mL | 1.0834 mL | 2.1667 mL |
References
- [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.
- [3] Yuzo Iwaki, et al. ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model. ACS Med Chem Lett. 2020 May 14;11(6):1335-1341.