Losmapimod (GW0856553X; SB0856553)

Alias: GW856553; Losmapimod; GSKAHAB; GW856553X; GW-856553; GW 856553, GSK-AHAB; GSK AHAB; GW-856553X; GW 856553X; SB856553; SB-856553; SB 856553

Cat No.:V0485 Purity: ≥98%

COA Product Data Instructions for use SDS

Losmapimod (formerly known as GSK-AHAB; GSK AHAB; GW856553,SB856553 or GW-856553X) is a novel, selective, potent, and orally bioavailable inhibitor of p38 MAPK (p38 mitogen-activated protein kinases) with potentialantidepressant, anti-hypertensive and anti-inflammatory activity.

Losmapimod (GW0856553X; SB0856553) Chemical Structure CAS No.: 585543-15-3
Product category: p38 MAPK

This product is for research use only, not for human use. We do not sell to patients.

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

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Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

LCMS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Losmapimod (formerly known as GSK-AHAB; GSK AHAB; GW856553, SB856553 or GW-856553X) is a novel, potent, and orally bioavailable inhibitor of p38 MAPK (p38 mitogen-activated protein kinases) with potential antidepressant, antihypertensive, and anti-inflammatory activity. With pKi values of 8.1 and 7.6 for p38α and p38β, respectively, it blocks p38 MAPK. Although further trials are needed to confirm the safety and effectiveness of losmapimod, it has potential antidepressant activity and has successfully completed Phase II human clinical trials for the treatment of depression. Also being researched for cardiovascular disease is losmapimod. There are currently two Phase II trials being conducted, one to investigate its effects in myocardial infarction (heart attack), and the other to treat COPD (chronic obstructive pulmonary disease).

Biological Activity I Assay Protocols (From Reference)

Targets	p38α (pKi = 8.1); p38β (pKi = 7.6)
ln Vitro	Losmapimod (GW856553X, GW856553, GSK-AHAB) is a selective, potent, and orally active p38 MAPK inhibitor.
ln Vivo	Losmapimod attenuates dyslipidemia, hypertension, cardiac remodeling, plasma renin activity (PRA), aldosterone, and interleukin-1beta (IL-1beta) after significantly enhancing survival, endothelial-dependent and -independent vascular relaxation, and indicators of renal function in spontaneously hypertensive stroke-prone rats (SHR-SP). [1]
Enzyme Assay	A ligand-displacement fluorescence polarization assay is used to determine the inhibition of p38β and p38.
Cell Assay	For two hours, cells were exposed to the drug at the indicated concentration.
Animal Protocol	Male SHR-SPs (n=70) were divided into five groups (n=14 per group) based on body weight and randomly assigned to one of five diets: 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 medications are taken orally by mixing with SFD. The conscious measurement of mean arterial blood pressure and heart rate is performed on a subgroup of animals from each group (n=6 per group) who have undergone anesthesia and have been surgically outfitted with radiotelemetry devices. Before the study begins, these animals are given at least 7 days to recover.
References	[1]. J Pharmacol Exp Ther . 2009 Sep;330(3):964-70. [2]. Dis Model Mech . 2022 Nov 1;15(11):dmm049516.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C22H26FN3O2

Molecular Weight

383.46

Exact Mass

383.20

Elemental Analysis

C, 68.91; H, 6.83; F, 4.95; N, 10.96; O, 8.34

CAS #

585543-15-3

Related CAS #

585543-15-3

Appearance

white solid powder

SMILES

CC1=C(C=C(C=C1F)C(=O)NC2CC2)C3=NC=C(C=C3)C(=O)NCC(C)(C)C

InChi Key

KKYABQBFGDZVNQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H26FN3O2/c1-13-17(9-15(10-18(13)23)21(28)26-16-6-7-16)19-8-5-14(11-24-19)20(27)25-12-22(2,3)4/h5,8-11,16H,6-7,12H2,1-4H3,(H,25,27)(H,26,28)

Chemical Name

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

Synonyms

GW856553; Losmapimod; GSKAHAB; GW856553X; GW-856553; GW 856553, GSK-AHAB; GSK AHAB; GW-856553X; GW 856553X; SB856553; SB-856553; SB 856553

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

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: 5mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04264442	Active Recruiting	Drug: Losmapimod	Facioscapulohumeral Muscular Dystrophy (FSHD)	Fulcrum Therapeutics	February 13, 2020	Phase 2
NCT04004000	Active Recruiting	Drug: Losmapimod	Facioscapulohumeral Muscular Dystrophy 1	Fulcrum Therapeutics	August 23, 2019	Phase 2
NCT05397470	Active Recruiting	Drug: Losmapimod Drug: Placebo oral tablet	Facioscapulohumeral Muscular Dystrophy (FSHD)	Fulcrum Therapeutics	June 16, 2022	Phase 3
NCT01756495	Active Recruiting	Drug: Losmapimod Drug: Moxifloxacin	Acute Coronary Syndrome	GlaxoSmithKline	January 10, 2013	Phase 1
NCT01039961	Completed	Drug: losmapimod Drug: losmapimod 1 mg	Cardiovascular Disease	GlaxoSmithKline	February 2, 2010	Phase 1

Biological Data

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

Losmapimod (GW856553X)

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.

Losmapimod (GW856553X)

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.

Losmapimod (GW856553X)

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.