| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
ONO8430506(ONO-8430506) is a novel and potent autotaxin inhibitor that enhances the antitumor effect of paclitaxel in a breast cancer model. Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biological functions, including smooth muscle contraction, cell motility, proliferation, and morphological change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma.
| ln Vitro |
Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), also name for autocrine motility factor, is a secreted enzyme that has lysophospholipase D activity. For recombinant human ATX/ENPP2 lysophospholipase D (LysoPLD) activity, ONO-8430506 has an IC50 of 5.1 nM in an experiment that uses a natural substrate (16:0-LPC) and a synthetic fluorogenic substrate (FS-3) [2]. With an IC50 of roughly 10 nM, ONO-8430506 efficiently suppresses the generation of lysophosphatidic acid (LPA) in both plasma-derived ATX/ENPP2 and recombinant ATX/ENPP2 from a variety of animal species [2].
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| ln Vivo |
For 21 days, ONO-8430506 (10 mg/kg/day; gavage) reduces lung metastasis and inhibits the initial growth of tumors [1]. ONO-8430506 decreased the early phases of the formation of breast tumors and the subsequent lung metastases by about 60% in a syngeneic orthotopic mice model [1]. Rats administered ONO-8430506 (oral; 30 mg/kg) show positive pharmacokinetics and long-lasting suppression of plasma lysophosphatidic acid production [2]. In breast cancer models, paclitaxel's anti-tumor activity is enhanced by ONO-8430506 (30 or 100 mg/kg) [3]. After oral dosing (rat 1, dog 1, and monkey 1), ONO-8430506 demonstrated moderate oral bioavailability (rat 51.6%, dog 71.1%, and monkey 30.8%) and Cmax (rat 261, dog 1670, and monkey 1) [3]. Because of its large distribution volume (1474, 1863) mL/kg and low plasma clearance (8.2, 4.7, and 5.8 mL/min/kg, respectively) following intravenous injection (0.3 mg/kg in rats, 0.3 mg/kg in dogs, and 0.3 mg/kg in monkeys), ONO-8430506 exhibits a terminal elimination half-life (rat 3.4, dog 8.9, and monkey 7.9 and 2275) [3].
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| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse, 8-10 weeks old (BALB/cAnNCrl) [1]
Doses: 10 mg/kg Route of Administration: daily gavage for 21 days; 10 μL/g Experimental Results:ONO-8430506 Tumor growth in treated mice caught up with the vehicle group on day 13; thereafter, primary tumor size was not Dramatically different from vehicle-treated mice. However, the number of metastatic nodules in the lungs was diminished by approximately 60% on day 21 of treatment with ONO-8430506. |
| 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. |
| Molecular Formula |
C27H28FN3O3
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|---|---|
| Molecular Weight |
461.5374
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| Exact Mass |
461.2115
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| Elemental Analysis |
C, 70.26; H, 6.12; F, 4.12; N, 9.10; O, 10.40
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| CAS # |
1354805-08-5
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| SMILES |
O=C(C1(C2)CCC2(CC(N(C3)CCC4=C3N(CC5=CC=C(F)C=C5)C6=NC=CC=C64)=O)CC1)O
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| InChi Key |
SGSFONPFVRRJLS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28FN3O3/c28-19-5-3-18(4-6-19)15-31-22-16-30(13-7-20(22)21-2-1-12-29-24(21)31)23(32)14-26-8-10-27(17-26,11-9-26)25(33)34/h1-6,12H,7-11,13-17H2,(H,33,34)
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| Chemical Name |
4-(2-(9-(4-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrrolo[2,3-b:5,4-c']dipyridin-7-yl)-2-oxoethyl)bicyclo[2.2.1]heptane-1-carboxylic acid
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| Synonyms |
ONO-8430506; ONO 8430506; ONO8430506
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~216.67 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1667 mL | 10.8333 mL | 21.6666 mL | |
| 5 mM | 0.4333 mL | 2.1667 mL | 4.3333 mL | |
| 10 mM | 0.2167 mL | 1.0833 mL | 2.1667 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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