ONO-8430506
Based on 1 Customer Validation
ONO-8430506 is an orally bioavailable and potent autotaxin (ATX)/ENPP2 inhibitor with the IC90 of 100 nM for ATX activity in mouse plasma.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.90%
- No. CAS: 1354805-08-5
- Fòrmula: C27H28FN3O3
- Peso molecular:461.53
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Almacenamiento:
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)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
IC50 & Target
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Autotaxin |
In Vitro
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)[2].
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[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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 Cmax (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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c mice, 8-10 wk old (BALB/cAnNCrl)[1]
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Dosage:10 mg/kg
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Administration:Gavaged daily for 21 days; 10 μL/g
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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%.
Chemical Information
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No. CAS 1354805-08-5
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Appearance Solid
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Peso molecular 461.53
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Fòrmula C27H28FN3O3
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SMILES
O=C(C12CCC(CC1)(C2)CC(N3CC4=C(CC3)C5=C(N4CC6=CC=C(C=C6)F)N=CC=C5)=O)O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
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)
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (216.67 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.42 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.42 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (276 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[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. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1667 mL | 10.8335 mL | 21.6671 mL | 54.1677 mL |
| 5 mM | 0.4333 mL | 2.1667 mL | 4.3334 mL | 10.8335 mL | |
| 10 mM | 0.2167 mL | 1.0834 mL | 2.1667 mL | 5.4168 mL | |
| 15 mM | 0.1444 mL | 0.7222 mL | 1.4445 mL | 3.6112 mL | |
| 20 mM | 0.1083 mL | 0.5417 mL | 1.0834 mL | 2.7084 mL | |
| 25 mM | 0.0867 mL | 0.4333 mL | 0.8667 mL | 2.1667 mL | |
| 30 mM | 0.0722 mL | 0.3611 mL | 0.7222 mL | 1.8056 mL | |
| 40 mM | 0.0542 mL | 0.2708 mL | 0.5417 mL | 1.3542 mL | |
| 50 mM | 0.0433 mL | 0.2167 mL | 0.4333 mL | 1.0834 mL | |
| 60 mM | 0.0361 mL | 0.1806 mL | 0.3611 mL | 0.9028 mL | |
| 80 mM | 0.0271 mL | 0.1354 mL | 0.2708 mL | 0.6771 mL | |
| 100 mM | 0.0217 mL | 0.1083 mL | 0.2167 mL | 0.5417 mL |
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