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Chemical Structure| 209410-46-8 同义名 : VX-745
CAS号 : 209410-46-8
货号 : A189058
分子式 : C19H9Cl2F2N3OS
纯度 : 99%+
分子量 : 436.262
MDL号 : MFCD09834070
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(27.51 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

30% PEG400+0.5% Tween80+5% propylene glycol+water 30 mg/mL suspension

生物活性
靶点

  • p38β

    p38β, IC50:220 nM

  • p38α

    p38α, IC50:10 nM
描述 p38α belongs to the family of mitogen-activated protein kinases. VX-745 is a potent p38α inhibitor with an IC50 value of 9 nM and it shows 20-fold selectivity for p38α over p38β. In human peripheral blood mononuclear cells, VX-745 blocks IL-1β and TNFα with IC50 values of 45 and 51 nM, respectively. It also effectively inhibited IL-1β and TNFα in whole blood with IC50 values of 150 and 180 nM, respectively. However, the IC50 values for the inhibition against CYPs 3A4, 2D6, 2C19, 2C9, and 1A2 were above 40 μM[1]. VX-745 (0.06 – 20 μM, 48h incubation) significantly reduced the release of IL-6 in the bone marrow stromal cells (BMSCs) from patients with multiple myeloma, and the peak inhibitory effect was observed when 2 μM VX-745 was used. VX-745 at 0.05, 0.5, and 5 μM inhibited TNF-α–induced increase of IL-6 in BMSCs. The cell growth of MM.1S, RPMI8226, and U266 cell lines were inhibited by VX-745 with an IC50 value of 10 μM[2]. In murine collagen-induced arthritis model, 20-day treatment of VX-745 at 2.5, 5, and 10 mg/kg (twice daily) showed 27%, 31%, and 44% improvement in the inflammatory scores, respectively, compared to control mice. It was also found that VX-745 treatment protected 32 – 39% bone and cartilage erosion[1].
作用机制 VX-745 is a selective p38α inhibitor. The 2,4-difluorophenyl ring of VX-745 occupies a hydrophobic pocket at T106 residue to make extensive van der Waals contacts with p38α. p38α also facilitates the binding of VX-745 by flipping the G110 backbone[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.29mL

0.46mL

0.23mL

11.46mL

2.29mL

1.15mL

22.92mL

4.58mL

2.29mL
参考文献

[1]Duffy JP, Harrington EM, et al. The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor. ACS Med Chem Lett. 2011 Jul 28;2(10):758-63.

[2]Hideshima T, Akiyama M, et al. Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Blood. 2003;101(2):703-5.

[3]Alam JJ, et al. Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats. J Alzheimers Dis. 2015;48(1):219-27.

[4]Brown KK, Heitmeyer SA, et al. P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22.