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Losmapimod(GW0856553X SB0856553)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Losmapimod(GW0856553X SB0856553)图片
CAS NO:585543-15-3
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)383.46
FormulaC22H26FN3O2
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
SynonymsGW856553; Losmapimod; GSKAHAB; GW856553X; GW-856553; GW 856553, GSK-AHAB; GSK AHAB; GW-856553X; GW 856553X; SB856553; SB-856553; SB 856553

Chemical Name: 6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-N-(2,2-dimethylpropyl)pyridine-3-carboxamide.

SMILES Code: O=C(C1=CC=C(C2=CC(C(NC3CC3)=O)=CC(F)=C2C)N=C1)NCC(C)(C)C

实验参考方法
In Vitro

In vitro activity: Losmapimod (formerly known as GW856553 or GW856553X) is a novel, selective, potent, and orally bioavailable inhibitor of p38 MAPK (p38 mitogen-activated protein kinases) with pKi of 8.1 and 7.6 for p38α and p38β, respectively. Losmapimod has potential antidepressant activity and it 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. Two Phase II trials, one to study its effects in myocardial infarction (heart attack) and another for the treatment of COPD (chronic obstructive pulmonary disease), are underway. 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 VivoIn 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 7.5 mg
ReferencesJ Pharmacol Exp Ther. 2009 Sep;330(3):964-70; Circulation. 2011 Feb 8;123(5):515-23.
生物活性


Structure (A) and activity profile (B) of GSK-AHAB, an aryl heteroaryl bis-carboxyamide series p38 MAPK inhibitor. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.


A, plasma concentration of GSK-AHAB and rofecoxib after 4 weeks of dietary dosing. B, COX1 and COX2 activity was determined in rofecoxib samples obtained at 8:00 AM. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.


Effects of treatment on survival (A) and mean arterial blood pressure (B) in stroke-prone, SHR-SPs placed on a SFD. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.


Urinary albumin excretion and creatinine clearance was determined at baseline before introduction of the SFD and at 2, 4, and 6 weeks of the study in all groups. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.


Vascular relaxation studies were performed in isolated thoracic aorta ring segments obtained from stroke-prone hypertensive rats maintained on a SFD for 8 weeks. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.



PRA and plasma concentrations of aldosterone and IL-1β were measured from blood samples obtained at 4 and 8 weeks of the study and in all groups. J Pharmacol Exp Ther. 2009 Sep;330(3):964-70.