Losmapimod (Synonyms: GSK-AHAB, Losmapimod, SB 856553) |
Catalog No.GC13717 |
p38 MAPK inhibitor, orally active
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 585543-15-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Male SHR-SPs (n=70) are randomly assigned according to body weight into five groups (n=14 per group): normal diet controls (ND), high salt-fat diet controls (SFD), SFD + GSK-AHAB (1.2 mg/kg/day), and SFD + GSK-AHAB (12 mg/kg/day) and SFD + MK 966 (18 mg/kg/day). All drugs are administered in the diet by mixing with the SFD. A subgroup of animals from each group (n=6 per group) are anesthetized and surgically instrumented with radiotelemetry units for the conscious measurement of mean arterial blood pressure and heart rate. These animals are allowed to recover for at least 7 days before the start of the study. |
References: [1]. Willette RN, 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. |
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 [1].
p38 mitogen-activated protein kinase (p38 MAPK) is an intracellular signaling kinase and plays an important role in regulating transcription and translation of the inflammatory response in macrophages and endothelial cells [2].
Losmapimod is an orally active p38 MAPK inhibitor. 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 [1]. 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 [2]. In patients with chronic obstructive pulmonary disease (COPD), losmapimod (7.5 mg twice daily) reduced plasma fibrinogen by 11% and was well tolerated [3].
References:
[1]. Willette RN, Eybye ME, Olzinski AR, 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, 330(3): 964-970.
[2]. Cheriyan J, Webb AJ, Sarov-Blat L, et al. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation., 2011, 123(5): 515-523.
[3]. Lomas DA, Lipson DA, Miller BE, et al. An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Pharmacol, 2012, 52(3): 416-424.
Cas No. | 585543-15-3 | SDF | |
Synonyms | GSK-AHAB, Losmapimod, SB 856553 | ||
Canonical SMILES | FC1=C(C)C(C(C=C2)=NC=C2C(NCC(C)(C)C)=O)=CC(C(NC3CC3)=O)=C1 | ||
Formula | C22H26FN3O2 | M.Wt | 383.46 |
Solubility | ≥ 19.15mg/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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.6078 mL | 13.0392 mL | 26.0783 mL |
5 mM | 0.5216 mL | 2.6078 mL | 5.2157 mL |
10 mM | 0.2608 mL | 1.3039 mL | 2.6078 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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.
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