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Losmapimod

drug
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Also known as FTX-1821FTX1821GSK-AHABGSKAHABGw-856553GW-856553XGw856553GW856553X

Summary

Losmapimod (CHEMBL1088752) is a phase-3 clinical-stage small-molecule EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor targeting MAPK14; indicated across 11 conditions including acute coronary syndrome and facioscapulohumeral muscular dystrophy.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 1 (MAPK14)
  • Indications: 11 conditions
  • Clinical trials: 24
  • Chemistry: 383.5 Da · C22H26FN3O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1088752
NameLosmapimod
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID11552706
ChEBICHEBI:131167
Molecular formulaC22H26FN3O2
Molecular weight383.5
InChIKeyKKYABQBFGDZVNQ-UHFFFAOYSA-N

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

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

ChEBI definition: A secondary carboxamide resulting from the formal condensation of the carboxy group of 6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]pyridine-3-carboxylic acid with the amino group of neopentylamine. It is a potent p38α/β mitogen activated protein kinase inhibitor which was previously in clinical trials for the treatment of facioscapulohumeral muscular dystrophy — trial now discontinued due to not achieving its primary endpoint.

Pharmacological roles (ChEBI): EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor, anti-inflammatory agent, cardioprotective agent, nootropic agent.

Also known as: FTX-1821, FTX1821, GSK-AHAB, GSKAHAB, Gw-856553, GW-856553X, Gw856553, GW856553X, Losmapimod, LOSMAPIMOD

Patent coverage: 337 distinct patent families (865 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 744 (86%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
MAPK14mitogen-activated protein kinase 14Inhibition8.19%Q16539

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Mitotic checkpoint serine/threonine-protein kinase BUB1, MAP kinase-activated protein kinase 2, Mitogen-activated protein kinase 14, cAMP-dependent protein kinase catalytic subunit gamma, Cytochrome P450 2C9, Mitogen-activated protein kinase 11, Long-chain-fatty-acid–CoA ligase 5, Serine/threonine-protein kinase 24.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 18 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
MAPK148.14Ki7.2nMCHEMBL_ACT_29099023
MAPK148.1Ki7.94nMCHEMBL_ACT_3260870
MAPK148.1Ki7.94nMCHEMBL_ACT_6230260
MAPK148.09Ki8.1nMCHEMBL_ACT_29099025
MAPK148.05Kd9nMCHEMBL_ACT_17915332
STK247.96Kd11nMCHEMBL_ACT_17941396
MAPK117.6Ki25.12nMCHEMBL_ACT_3261937
MAPK117.6Ki25.12nMCHEMBL_ACT_6230261
MAPK147.6IC5025.12nMCHEMBL_ACT_6230263
MAPKAPK27.57Kd27nMCHEMBL_ACT_17916677
MAPK117.54Kd29nMCHEMBL_ACT_17915073
MAPK147.2Ki63.1nMCHEMBL_ACT_6230298
MAPK147IC50100nMCHEMBL_ACT_6230262
ACSL55.77Kd1690nMCHEMBL_ACT_17880158
BUB15.72Kd1921nMCHEMBL_ACT_17886281
MAPK145.26IC505500nMCHEMBL_ACT_27865472

Target pathways

Aggregated over 1 target gene(s): MAPK14.

Top Reactome pathways

78 total, by targets touching each:

PathwayTargetsGenes
Hemostasis1MAPK14
Developmental Biology1MAPK14
Cytokine Signaling in Immune system1MAPK14
Mitochondrial biogenesis1MAPK14
Signal Transduction1MAPK14
Disease1MAPK14
Toll Like Receptor 4 (TLR4) Cascade1MAPK14
MyD88:MAL(TIRAP) cascade initiated on plasma membrane1MAPK14
MyD88-independent TLR4 cascade1MAPK14
Signaling by NTRKs1MAPK14
Signalling to RAS1MAPK14
Toll Like Receptor 9 (TLR9) Cascade1MAPK14
Toll Like Receptor 10 (TLR10) Cascade1MAPK14
Toll Like Receptor 3 (TLR3) Cascade1MAPK14
Toll Like Receptor 5 (TLR5) Cascade1MAPK14
Toll Like Receptor TLR1:TLR2 Cascade1MAPK14
Toll Like Receptor 7/8 (TLR7/8) Cascade1MAPK14
Toll Like Receptor TLR6:TLR2 Cascade1MAPK14
Innate Immune System1MAPK14
Immune System1MAPK14
NOD1/2 Signaling Pathway1MAPK14
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways1MAPK14
Toll-like Receptor Cascades1MAPK14
p38MAPK events1MAPK14
Toll Like Receptor 2 (TLR2) Cascade1MAPK14
Organelle biogenesis and maintenance1MAPK14
Signaling by NTRK1 (TRKA)1MAPK14
Signalling to ERKs1MAPK14
Signaling by VEGF1MAPK14
Signaling by Rho GTPases1MAPK14

Dominant GO biological processes

GO termTargets
DNA damage checkpoint signaling1
MAPK cascade1
cell morphogenesis1
cartilage condensation1
angiogenesis1
osteoblast differentiation1
placenta development1
response to dietary excess1
chondrocyte differentiation1
negative regulation of inflammatory response to antigenic stimulus1
glucose metabolic process1
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
apoptotic process1
chemotaxis1

Indications & clinical

Indications

11 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
acute coronary syndrome3MONDO:0005542EFO:0005672
facioscapulohumeral muscular dystrophy3MONDO:0001347Orphanet:269
severe acute respiratory syndrome3MONDO:0005091MONDO:0100096
neuralgia2MONDO:0021667EFO:0005762
focal segmental glomerulosclerosis2MONDO:0100313EFO:0004236
chronic obstructive pulmonary disease2MONDO:0005002EFO:0000341
atherosclerosis2MONDO:0005311EFO:0003914
rheumatoid arthritis2MONDO:0008383EFO:0000685
major depressive disorder2MONDO:0002009MONDO:0002009
cardiovascular disorder1MONDO:0004995EFO:0000319

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 24.

Phase distribution

PhaseTrials
PHASE217
PHASE15
PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04511819PHASE3TERMINATEDLosmapimod Safety and Efficacy in COVID-19
NCT05397470PHASE3TERMINATEDEfficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
NCT00256919PHASE2COMPLETEDSingle Dose Study Of GW856553 On A Protein That Is An Indicator For Rheumatoid Arthritis (RA)
NCT00392587PHASE2COMPLETEDA Study To Investigate The Effects Of GW856553 On Patients With COPD (Chronic Obstructive Pulmonary Disease)
NCT00393146PHASE2COMPLETEDA Study To Investigate The Effect Of 28 Days Of Dosing With GW856553 On Patients With Rheumatoid Arthritis
NCT00474864PHASE2COMPLETEDStudy To Evaluate The Effects Of GW856553 On Endothelial Function/Vascular Compliance In Subjects With Dyslipidaemia.
NCT00569062PHASE2TERMINATEDA Study of GW856553X For the Treatment of Depression
NCT00633022PHASE2COMPLETEDA Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging
NCT00642148PHASE2COMPLETEDA 12 Week Study To Assess Efficacy And Safety Of GW856553 In Subjects With Chronic Obstructive Pulmonary Disease (COPD)
NCT00910962PHASE2COMPLETEDA Study to Evaluate the Safety of 12 Weeks of Dosing With GW856553 and Its Effects on Inflammatory Markers, Infarct Size, and Cardiac Function in Subjects With Myocardial Infarction Without ST-segment Elevation
NCT00969059PHASE2COMPLETEDStudy in Neuropathic Pain Patients With Peripheral Nerve Injury
NCT00976560PHASE2COMPLETEDClinical Study to Test a New Drug to Treat Major Depression
NCT01218126PHASE2COMPLETEDRandomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-centre, Dose Ranging Study to Evaluate the Efficacy and Safety of Losmapimod Tablets Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD).
NCT01541852PHASE2COMPLETEDLosmapimod in Chronic Obstructive Pulmonary Disease Patients Stratified by Fibrinogen.
NCT02000440PHASE2COMPLETEDA Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS)
NCT02299375PHASE2COMPLETEDSafety and Efficacy Study of Losmapimod (GW856553) in Frequently Exacerbating Participants With Chronic Obstructive Pulmonary Disease (COPD)
NCT04003974PHASE2COMPLETEDEfficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT04004000PHASE2TERMINATEDEvaluation of Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments of Losmapimod for FSHD1 With Extension
NCT04264442PHASE2TERMINATEDEfficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)
NCT00517543PHASE1COMPLETEDA Study to Examine the Effect of Particle Size on Bioequivalence and Bioavailability
NCT00549653PHASE1COMPLETEDA Study Investigating Blood Concentrations Of Rosuvastatin When Co-administered With GW856553 In Healthy Men
NCT00599612PHASE1COMPLETEDTo Assess the Excretion Balance and Pharmacokinetics of a Single Oral Dose of [14C]GW856553 in Healthy Adult Males
NCT01039961PHASE1COMPLETEDPK Study of IV Formulation of GW856553
NCT01756495PHASE1COMPLETEDA Study to Evaluate the Effect of Losmapimod on Cardiac Conduction as Compared to Placebo and Moxifloxacin

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

65 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
AFATINIBChEMBL + PubChemPhase 4 (approved)MAPK14
REGORAFENIBChEMBL + PubChemPhase 4 (approved)MAPK14
3,3’,4’,5-TETRACHLOROSALICYLANILIDEChEMBLPhase 4 (approved)MAPK14
BENZBROMARONEChEMBLPhase 4 (approved)MAPK14
BITHIONOLChEMBLPhase 4 (approved)MAPK14
CELECOXIBChEMBLPhase 4 (approved)MAPK14
DASATINIBChEMBLPhase 4 (approved)MAPK14
DIETHYLSTILBESTROLChEMBLPhase 4 (approved)MAPK14
ENCORAFENIBChEMBLPhase 4 (approved)MAPK14
ETORICOXIBChEMBLPhase 4 (approved)MAPK14
GEFITINIBChEMBLPhase 4 (approved)MAPK14
HEXACHLOROPHENEChEMBLPhase 4 (approved)MAPK14
IMATINIBChEMBLPhase 4 (approved)MAPK14
ISOTRETINOINChEMBLPhase 4 (approved)MAPK14
LENVATINIBChEMBLPhase 4 (approved)MAPK14
MIFEPRISTONEChEMBLPhase 4 (approved)MAPK14
MONTELUKASTChEMBLPhase 4 (approved)MAPK14
NALFURAFINEChEMBLPhase 4 (approved)MAPK14
NELFINAVIRChEMBLPhase 4 (approved)MAPK14
NILOTINIBChEMBLPhase 4 (approved)MAPK14
PONATINIBChEMBLPhase 4 (approved)MAPK14
QUIZARTINIBChEMBLPhase 4 (approved)MAPK14
SORAFENIBChEMBLPhase 4 (approved)MAPK14
TANNIC ACIDChEMBLPhase 4 (approved)MAPK14
TOVORAFENIBChEMBLPhase 4 (approved)MAPK14
TRIBROMSALANChEMBLPhase 4 (approved)MAPK14
VANDETANIBChEMBLPhase 4 (approved)MAPK14
ZAFIRLUKASTChEMBLPhase 4 (approved)MAPK14
ARRY-797ChEMBLPhase 3MAPK14
EPIGALOCATECHIN GALLATEChEMBLPhase 3MAPK14
LINIFANIBChEMBLPhase 3MAPK14
PERIFOSINEChEMBLPhase 3MAPK14
TIRILAZADChEMBLPhase 3MAPK14
BAFETINIBChEMBLPhase 2MAPK14
BMS-582949ChEMBLPhase 2MAPK14
CEP-32496ChEMBLPhase 2MAPK14
CLOSANTELChEMBLPhase 2MAPK14
DIELDRINChEMBLPhase 2MAPK14
DORAMAPIMODChEMBLPhase 2MAPK14
FENBENDAZOLEChEMBLPhase 2MAPK14
FILAMINASTChEMBLPhase 2MAPK14
FORETINIBChEMBLPhase 2MAPK14
GALUNISERTIBChEMBLPhase 2MAPK14
GOLVATINIBChEMBLPhase 2MAPK14
ILORASERTIBChEMBLPhase 2MAPK14
IODOQUINOLChEMBLPhase 2MAPK14
ITX-5061 FREE BASEChEMBLPhase 2MAPK14
JNJ-49095397ChEMBLPhase 2MAPK14
MW-150ChEMBLPhase 2MAPK14
NAFENOPINChEMBLPhase 2MAPK14
NEFLAMAPIMODChEMBLPhase 2MAPK14
OSI-632ChEMBLPhase 2MAPK14
PAMAPIMODChEMBLPhase 2MAPK14
PEXMETINIBChEMBLPhase 2MAPK14
PH-797804ChEMBLPhase 2MAPK14
REBASTINIBChEMBLPhase 2MAPK14
TAK-715ChEMBLPhase 2MAPK14
TALMAPIMODChEMBLPhase 2MAPK14
TANZISERTIBChEMBLPhase 2MAPK14
TOP-1288ChEMBLPhase 2MAPK14

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot