product name Losmapimod (GW856553X)
Description: Losmapimod, also know as GW856553 or GW856553X, is a selective, potent, and orally bioavailable p38 MAPK inhibitor with pKi of 8.1 and 7.6 for p38α and p38β, respectively. Losmapimod has completed Phase II human clinical trials for the treatment of depression although its safety and efficacy have yet to be proven in further trials. Losmapimod is also being studied for cardiovascular disease. A Phase II trial to study its effects in myocardial infarction (heart attack) is ongoing.
References: J Pharmacol Exp Ther. 2009 Sep;330(3):964-70; Circulation. 2011 Feb 8;123(5):515-23.
383.46
Formula
C22H26FN3O2
CAS No.
585543-15-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 76 mg/mL (198.2 mM)
Water: <1 mg/mL
Ethanol: 41 mg/mL (106.9 mM)
Solubility (In vivo)
4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL
Synonyms
GW856553, GSK-AHAB, GW856553X
other peoduct :
| In Vitro |
In vitro activity: In spontaneously hypertensive stroke-prone rats (SHR-SP), Losmapimod significantly improves survival, endothelial-dependent and -independent vascular relaxation, and indices of renal function, and subsequently attenuates dyslipidemia, hypertension, cardiac remodeling, plasma renin activity (PRA), aldosterone, and interleukin-1beta (IL-1beta). Kinase Assay: Losmapimod (GW856553, GW856553X, GSK-AHAB) is a potent and selective inhibitor of p38 MAPK with pKi values of 8.1 and 7.6 for p38α and p38β, respectively. Cell Assay: In SHR-SPs receiving a salt-fat diet (SFD), chronic treatment with GSK-AHAB significantly and dose-dependently improved survival, endothelial-dependent and -independent vascular relaxation, and indices of renal function, and it attenuated dyslipidemia, hypertension, cardiac remodeling, plasma renin activity (PRA), aldosterone, and interleukin-1beta (IL-1beta). |
|---|---|
| In Vivo | In the spontaneously hypertensive stroke-prone rats (SHR-SPs) with a salt-fat diet, GSK-AHAB significantly improved survival and renal function in a dose-dependent way and induced vascular relaxation. Also, GSK-AHAB attenuated hypertension, cardiac remodeling, dyslipidemia, plasma renin activity (PRA), interleukin-1 (IL-1) and aldosterone. In patients with hypercholesterolemia, losmapimod improved acetylcholine, sodium nitroprusside and NG-monomethyl-L-arginine (L-NMMA) responses by 25%, 20% and 10%, respectively. Also, losmapimod reduced C-reactive protein (a systemic inflammatory marker) by 57%. These results suggested that losmapimod improved NO-mediated vasodilatation and inhibited inflammation. In patients with chronic obstructive pulmonary disease (COPD), losmapimod (7.5 mg twice daily) reduced plasma fibrinogen by 11% and was well tolerated. |
| Animal model | Hypertensive stroke-prone rats (SHR-SPs) |
| Formulation & Dosage | |
| References | J Pharmacol Exp Ther. 2009 Sep;330(3):964-70; Circulation. 2011 Feb 8;123(5):515-23. |
