LOSMAPIMOD

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H26FN3O2
Molecular Weight	383.4591
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=KKYABQBFGDZVNQ-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C22H26FN3O2
Molecular Weight	383.4591
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800023191
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19556450

Losmapimod (GW856553, GSK-AHAB) is a selective, potent, and orally active p38 MAPK (p38α and p38β isoforms) inhibitor that acts by competing for the kinase ATP binding site. GlaxoSmithKline (GSK) is developing oral losmapimod for the treatment of acute coronary syndromes (phase III), chronic obstructive pulmonary disease (phase II) and primary focal segmental glomerulosclerosis (phase II). Oral losmapimod was in phase II development for the treatment of rheumatoid arthritis and major depressive disorder; however, it appears that development for these indications has been discontinued. No further development was reported for atherosclerosis, dyslipidaemia and neuropathic pain.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
MAP kinase p38 alpha 34 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19556450	Inhibitor 8504		8.1 null [pKi]
MAP kinase p38 beta 11 Target ID: CHEMBL3961 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19556450	Inhibitor 8504		7.6 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Acute coronary syndrome 33 Sources: http://adisinsight.springer.com/drugs/800023191	Primary	Phase III 665	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 175 Sources: http://adisinsight.springer.com/drugs/800023191	Primary	Phase II 1147	Unknown Approved Use Unknown
Focal segmental glomerulosclerosis 1 Sources: http://adisinsight.springer.com/drugs/800023191	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
45.9 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23215699	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		LOSMAPIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
528 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23215699	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		LOSMAPIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.439 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23215699	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		LOSMAPIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 961 OAT1 725 CYPs 29 P-gp 1741 OATP1B1 1079 OCT2 779 BCRP 910 CYP1A2 2153 OAT3 747 CYP2C19 2057	OATP1B3 435 OAT1 395 CYPs 33 P-gp 2052 OATP1B1 503 OCT2 434

Drug as perpetrator

Target	Modality	Activity
CYPs 35	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 79.4328 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 >78.4328 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 >79.4328 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 >79.4328 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680217	yes [IC50 10.684 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	yes
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	yes

Drug as victim

Target	Modality	Activity
CYPs 33	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OAT1 395	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B1 503	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B3 435	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00ECUM	https://www.1pchem.com/search?query=1P00ECUM
A2B Chem	AG69038	http://a2bchem.com/prod/AG69038
AChemBlock	Q65752	http://www.achemblock.com/catalogsearch/result/?q=Q65752
AK Scientific	2523AH	https://aksci.com/item_detail.php?cat=2523AH
AOBIOUS INC	AOB87105	http://aobious.com/aobious/search?search_query=AOB87105
ApexBio Technology	B4620	https://www.apexbt.com/catalogsearch/result/?q=B4620
AstaTech	40669	http://astatechinc.com/CPSResult.php?CRNO=40669
BLD Pharm	BD630778	http://www.bldpharm.com/search/Search.html?keyword=BD630778
Cayman Chemical	13614	http://www.caymanchem.com/app/template/Product.vm/catalog/13614
Chem Scene	CS-3235	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3235
ChemShuttle	141881	https://www.chemshuttle.com/catalogsearch/result/?q=141881
Debye Scientific	DA-33431	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-33431
eMolecules	49839460	https://orderbb.emolecules.com/search/#?query=49839460
eMolecules	50763949	https://orderbb.emolecules.com/search/#?query=50763949
Excenen	EX-A486	http://www.excenen.com/searchresultlist.php?id=EX-A486
KeyOrganics	GE-0056	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=GE-0056
KeyOrganics	HE-0090	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=HE-0090
Lab Network	LN01306044	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01306044
mcule	MCULE-4783102620	https://mcule.com/MCULE-4783102620/
MedChem Express	HY-10402	https://www.medchemexpress.com/search.html?q=HY-10402&ft=&fa=&fp=
Molnova	M15150	https://www.molnova.com/en/serch-list.html?keywords=M15150
MolPort	MolPort-009-194-138	https://www.molport.com/shop/molecule-link/MolPort-009-194-138
Ryan Scientific	Tizoxanide	https://ryansci.com/products?q=Tizoxanide&list_q=&search_type=exact
Selleck Chemicals	S7215	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7215
ShangHai Biochempartner	BCP09909	http://www.biochempartner.com/search_BCP09909
TargetMol	T2277	https://www.targetmol.com/search?keyword=T2277

PubMed

Title	Date	PubMed
Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease.	2011-11-24	21888439
p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression.	2009-10-22	19772287

Patents

Sample Use Guides

In Vivo Use Guide

Oral losmapimod 2.5 - 20 mg twice daily. A single IV infusion of losmapimod (3 mg) may potentially serve as an initial loading dose in acute coronary syndrome as rapid exposure is achieved.

Route of Administration: Other

In Vitro Use Guide

0.1 and 1 nM Losmapimod (GW856553) synergistically increased the inhibitory effect of dexamethasone on LPS-induced CXCL8 release in peripheral blood mononuclear cells from patients with chronic obstructive pulmonary disease

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:22:20 GMT 2025` Edited by `admin` on `Mon Mar 31 18:22:20 GMT 2025`
Record UNII	F2DQF16BXE
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

GSKAHAB

Preferred Name

English

LOSMAPIMOD

Official Name

English

GW-856553X

Code

English

GW856553X

Code

English

FTX1821

Code

English

LOSMAPIMOD [USAN]

Common Name

English

Losmapimod [WHO-DD]

Common Name

English

6-(5-((CYCLOPROPYLAMINO)CARBONYL)-3-FLUORO-2-METHYLPHENYL)-N-(2,2-DIMETHYLPROPYL)-3-PYRIDINECARBOXAMIDE

Systematic Name

English

3-PYRIDINECARBOXAMIDE, 6-(5-((CYCLOPROPYLAMINO)CARBONYL)-3-FLUORO-2-METHYLPHENYL)-N-(2,2-DIMETHYLPROPYL)-

Systematic Name

English

FTX-1821

Code

English

losmapimod [INN]

Common Name

English

GW856553

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2149