产品说明书

Losmapimod

Print
Chemical Structure| 585543-15-3 同义名 : GSK-AHAB;GW856553X;GW856553;SB856553
CAS号 : 585543-15-3
货号 : A100781
分子式 : C22H26FN3O2
纯度 : 99%+
分子量 : 383.459
MDL号 : MFCD16619322
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(65.2 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

无水乙醇: 30 mg/mL(78.24 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 6 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • p38β

    p38β, pKi:7.6

  • p38α

    p38α, pKi:8.1
描述 Mitogen-activated protein kinase p38 is a stress-induced intracellular kinase that plays essential roles in the regulation of cellular responses, including migration, cytokine expression, and contraction. Losmapimod is a potent, orally active inhibitor of p38α and p38β with pKi values of 8.1 and 7.6, respectively[1]. In gefitinib-resistant cells (HCC827GR and H1975), treatment of 1 μM losmapimod for 10 hours inhibited gefitinib-induced phosphorylation of STAT3 and expressions of p21 and cyclin D1. Combined treatment of gefitinib (1 μM) and losmapimod (1 μM) significantly suppressed anchorage-independent cell growth and proliferation in NSCLC cells[2]. Spontaneously hypertensive stroke-prone rat (SHR-SP) placed on high salt-fat diet (SFD) for 8 weeks showed 50% survival rate and increased mean blood pressure. Dietary administration of losmapimod (1.2 and 12 mg/kg/day doses) significantly elevated the survival rate. Animals receiving 12 mg/kg/day losmapimod also showed suppressed mean blood pressure compared to untreated SFD-fed rats. Treatment of losmapimod (1.2 and 12 mg/kg/day doses) for 6 weeks attenuated SFD-induced increase in urine flow, FENa, albumin excretion, creatinine clearance, and kidney weight. Rats administered with 12 mg/kg/day losmapimod showed reduced left ventricular mass and wall thickness compared with untreated SFD-fed rats. Endothelial-dependent and endothelium-independent vasorelaxation were also improved by losmapimod treatment at a dose-dependent manner[1].
作用机制 Losmapimod selectively and potently inhibits p38 via competing for the kinase ATP binding site[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.61mL

0.52mL

0.26mL

13.04mL

2.61mL

1.30mL

26.08mL

5.22mL

2.61mL
参考文献

[1]Willette RN, Eybye ME, et al. Differential effects of p38 mitogen-activated protein kinase and cyclooxygenase 2 inhibitors in a model of cardiovascular disease. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.

[2]Yeung YT, Yin S, et al. Losmapimod Overcomes Gefitinib Resistance in Non-small Cell Lung Cancer by Preventing Tetraploidization. EBioMedicine. 2018.