VX-702 |
| Catalog No.GC17508 |
VX-702 est un inhibiteur hautement sélectif de p38α MAPK, 14 fois plus puissant contre p38α que p38β.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 745833-23-2
Sample solution is provided at 25 µL, 10mM.
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VX-702 is a selective inhibitor of p38α MAPK with IC50 value ranges from 4 nM to 20 nM [1].
P38 mitogen-activated protein kinases (p38 MAPK), also named as MAPK14, are a class of mitogen-activated protein kinases and play an important role in a signaling cascade controlling cellular responses to cytokines and stress [1-3].
VX-702 is a potent p38α MAPK inhibitor and is designed as for greater affinity and greater selectivity compared with the first reported p38α MAPK inhibitors. When tested with PLTs (platelets), VX-702 caused better maintenance of PLT mitochondrial, functional, structural and metabolic parameters during 7 days storage and restored PLTs properties following an extended interruption of agitation to levels of continuously agitated PLTs [2, 4].
In the isolated perfused rat kidney (IPRK) model, administration of VX-702 at a range of doses between 100 and 600 ng/mL showed linear excretion and the clearance data were consistent with net reabsorption by the kidney. Further, VX-702 was showed not a substrate for renal organic anion and organic cation transport systems [3].
References:
[1]. Kuliopulos, A., R. Mohanlal, and L. Covic, Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost, 2004. 92(6): p. 1387-93.
[2]. Skripchenko, A., et al., An inhibition of p38 mitogen activated protein kinase delays the platelet storage lesion. PLoS One, 2013. 8(8): p. e70732.
[3]. Tamhane, M., et al., Comparative renal excretion of VX-702, a novel p38 MAPK inhibitor, and methotrexate in the perfused rat kidney model. Drug Dev Ind Pharm, 2010. 36(3): p. 315-22.
[4]. Wagner, S.J., et al., Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16 degrees C by a p38MAPK inhibitor, VX-702. Vox Sang, 2015. 108(3): p. 226-32.
| Cell experiment [1]: | |
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Cell lines |
blood platelets |
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Preparation method |
The solubility of this compound in DMSO is > 20.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
IC50: 4 to 20 nM |
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Applications |
In an ex vivo blood assay primed with LPS, VX-702 dose-dependently inhibited the production of IL-6, IL-1β and TNFα with the IC50 of 59, 122 and 99 ng/ml, respectively. In gel-filtered platelets were prepared from healthy individuals, the activation was completely or partially inhibited by pre-incubation with 1 μM of VX-702 (IC50 = 4 to 20 nM). VX-702 had no effect on platelet aggregation induced by any of the p38 MAPK agonists, such as thrombin, SFLLRN, AYPGKF and collagen, in the presence or absence of platelet inhibitors, such as aspirin, heparin or apyrase. VX-702 did not directly cause platelet aggregation or induce Ca2+ mobilization, or affect basal aggregation induced by shear stress. VX-702 did not significantly affect platelet function and would not be expected to contribute to an elevated risk of hematological side effects in treated patients. |
| Animal experiment [1]: | |
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Animal models |
Mouse collagen-induced arthritis |
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Dosage form |
Oral administration, 0.1 mg/kg, 5 mg/kg, twice daily |
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Application |
VX-702 (0.1 mg/kg twice daily) was equivalent to methotrexate (a commonly used disease modifying antirheumatic drug [DMARD]; also at 0.1 mg/kg) in mouse collagen-induced arthritis. VX-702 (5 mg/kg, twice daily) was found to be equivalent to prednisolone (10 mg/kg, once daily) in the same model, as measured by the percentage inhibition of wrist joint erosion and an inflammation score. Male Sprague Dawley rats with myocardial damage after ischemia-reperfusion injury were randomized to receive either vehicle or VX-702 (5 or 50 mg/kg). The results suggested that phosphor MK2 was markedly increased in the ischemic zone tissue compared with the non-ischemic zone tissue in the vehicle group. This effect was dose-dependently reduced in the VX-702 groups. VX-702 selectively inhibited activation of p38 MAPK after ischemia, with no effects on ERKs and JNKs. The MI/AAR ratio was significantly reduced in the 50-mg/kg group compared with the other two groups. Oral administration of VX-702 reduced myocardial damage after ischemia-reperfusion injury. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Ding C. Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome[J]. Current opinion in investigational drugs, 2006, 7(11): 1020-1025. |
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| Cas No. | 745833-23-2 | SDF | |
| Chemical Name | 6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)pyridine-3-carboxamide | ||
| Canonical SMILES | C1=CC(=C(C(=C1)F)N(C2=NC(=C(C=C2)C(=O)N)C3=C(C=C(C=C3)F)F)C(=O)N)F | ||
| Formula | C19H12F4N4O2 | M.Wt | 404.33 |
| Solubility | ≥ 20.2mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4732 mL | 12.3661 mL | 24.7323 mL |
| 5 mM | 0.4946 mL | 2.4732 mL | 4.9465 mL |
| 10 mM | 0.2473 mL | 1.2366 mL | 2.4732 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)
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