LOSMAPIMOD

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(F)C=C(C=C1C2=CC=C(C=N2)C(=O)NCC(C)(C)C)C(=O)NC3CC3

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 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19556450	Inhibitor 8297		8.1 null [pKi]
MAP kinase p38 beta 11 Target ID: CHEMBL3961 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19556450	Inhibitor 8297		7.6 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Acute coronary syndrome 33 Sources: http://adisinsight.springer.com/drugs/800023191	Primary	Phase III 656	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 174 Sources: http://adisinsight.springer.com/drugs/800023191	Primary	Phase II 1132	Unknown Approved Use Unknown
Focal segmental glomerulosclerosis 1 Sources: http://adisinsight.springer.com/drugs/800023191	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 706 OAT1 599 CYPs 22 P-gp 1461 OATP1B1 788 OCT2 647 BCRP 699 CYP1A2 1524 OAT3 642 CYP2C19 1478	OATP1B3 350 OAT1 326 CYPs 33 P-gp 1537 OATP1B1 406 OCT2 355

Drug as perpetrator

Target	Modality	Activity
CYPs 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 .79.4328 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 >78.4328 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 >79.4328 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19772287/	unlikely [IC50 >79.4328 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680217	yes [IC50 10.684 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	yes
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	yes

Drug as victim

Target	Modality	Activity
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/33931884/	no
P-gp 1537	substrate 3367 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
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
MedChem Express	HY-10402	https://www.medchemexpress.com/search.html?q=HY-10402&ft=&fa=&fp=
MolPort	MolPort-009-194-138	https://www.molport.com/shop/molecule-link/MolPort-009-194-138
Molnova	M15150	https://www.molnova.com/en/serch-list.html?keywords=M15150
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
eMolecules	49839460	https://orderbb.emolecules.com/search/#?query=49839460
eMolecules	50763949	https://orderbb.emolecules.com/search/#?query=50763949
mcule	MCULE-4783102620	https://mcule.com/MCULE-4783102620/

PubMed

Title	Date	PubMed
Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease.	2011 Nov 24	21888439

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 `Fri Dec 15 16:13:23 GMT 2023` Edited by `admin` on `Fri Dec 15 16:13:23 GMT 2023`
Record UNII	F2DQF16BXE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LOSMAPIMOD

Official Name

English

GW-856553X

Code

English

GSKAHAB

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