VX-702
(Synonyms: 6-[(氨基羰基)(2,6-二氟苯基)氨基]-2-(2,4-二氟苯基)-3-吡啶甲酰胺) 目录号 : GC17508
An inhibitor of p38 MAP kinases
Cas No.:745833-23-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
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]: | |
|
Cell lines |
blood platelets |
|
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. |
|
Reacting condition |
IC50: 4 to 20 nM |
|
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]: | |
|
Animal models |
Mouse collagen-induced arthritis |
|
Dosage form |
Oral administration, 0.1 mg/kg, 5 mg/kg, twice daily |
|
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. |
|
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. |
|
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. |
|
| Cas No. | 745833-23-2 | SDF | |
| 别名 | 6-[(氨基羰基)(2,6-二氟苯基)氨基]-2-(2,4-二氟苯基)-3-吡啶甲酰胺 | ||
| 化学名 | 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 | ||
| 分子式 | C19H12F4N4O2 | 分子量 | 404.33 |
| 溶解度 | ≥ 20.2mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet