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Losmapimod (Synonyms: GSK-AHAB, Losmapimod, SB 856553)

Catalog No.GC13717

p38 MAPK inhibitor, orally active

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Losmapimod Chemical Structure

Cas No.: 585543-15-3

Size Price Stock Qty
10mM (in 1mL DMSO)
$67.00
In stock
10mg
$47.00
In stock
50mg
$192.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

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.
[2]. Zhang XM, et al. Suppression of mitochondrial fission in experimental cerebral ischemia: The potential neuroprotective target of p38 MAPK inhibition. Neurochem Int. 2015 Nov;90:1-8.

Background

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.

Chemical Properties

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.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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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
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Average Rating: 5 ★★★★★ (Based on Reviews and 29 reference(s) in Google Scholar.)

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