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Momelotinib

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Also known as CYT-0387CYT-11387Cyt-387CYT387GS-0387SID137275866MOMELOTINIB (CYT387)Cytopia

Summary

Momelotinib (CHEMBL1078178) is an approved small-molecule EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor (ATC L01EJ04) targeting ACVR1, JAK1, and JAK2; indicated across 8 conditions including primary myelofibrosis and neoplasm.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EJ04
  • Targets: 5 (ACVR1, JAK1, JAK2…)
  • Indications: 8 conditions
  • Clinical trials: 24
  • Chemistry: 414.5 Da · C23H22N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1078178
NameMomelotinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID25062766
ChEBICHEBI:91407
ATCL01EJ04
Molecular formulaC23H22N6O2
Molecular weight414.5
InChIKeyZVHNDZWQTBEVRY-UHFFFAOYSA-N

SMILES: C1COCCN1C2=CC=C(C=C2)NC3=NC=CC(=N3)C4=CC=C(C=C4)C(=O)NCC#N

IUPAC name: N-(cyanomethyl)-4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]benzamide

ChEBI definition: A benzamide obtained by formal condensation of the carboxy group of 4-{2-[4-(morpholin-4-yl)anilino]pyrimidin-4-yl}benzoic acid with the primary amino group of aminoacetonitrile. It is an ATP-competitive JAK1/JAK2 inhibitor with IC50 of 11 nM and 18 nM, respectively. Used for the treatment of patients with intermediate- or high-risk myelofibrosis.

Pharmacological roles (ChEBI): EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, antineoplastic agent, anti-anaemic agent, apoptosis inducer.

Also known as: CYT-0387, CYT-11387, Cyt-387, CYT-387, CYT387, GS-0387, Momelotinib, MOMELOTINIB, SID137275866, MOMELOTINIB (CYT387), Momelotinib (CYT387), Cytopia

Parent form; salt/anhydrous children: CHEMBL2219411, CHEMBL6068336

Patent coverage: 1,300 distinct patent families (3,481 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,052 (88%) 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
ACVR1activin A receptor type 1Inhibition8.080.2%Q04771
JAK1Janus kinase 1Inhibition7.572.8%P23458
JAK2Janus kinase 2Inhibition8.850.7%O60674
JAK3Janus kinase 3Inhibition6.810.6%P52333
TYK2tyrosine kinase 2Inhibition7.70.8%P29597

Broader ChEMBL bioactivity targets: 48 (assay-derived). Sample: Serine/threonine-protein kinase ICK, Tyrosine-protein kinase JAK2, Tyrosine-protein kinase JAK3, Mitogen-activated protein kinase 8, Cyclin-dependent kinase 6, Serine/threonine-protein kinase D3, Mitogen-activated protein kinase 10, Calcium/calmodulin-dependent protein kinase type II subunit delta, Tyrosine-protein kinase JAK1, Tyrosine-protein kinase JAK2.

Bioactivity

ChEMBL activities: 107 potent at pChembl ≥ 5 of 107 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
JAK18.8IC501.6nMCHEMBL_ACT_26008536
Q6ZSR98.52Kd3nMCHEMBL_ACT_17933688
AAK18.4Kd4nMCHEMBL_ACT_17878242
JAK28.35Kd4.5nMCHEMBL_ACT_25839913
JAK28.17Kd6.7nMCHEMBL_ACT_25839812
ACVR18.1IC508nMCHEMBL_ACT_17796703
TYK28.04Kd9.2nMCHEMBL_ACT_25839832
JAK17.96IC5011nMCHEMBL_ACT_14545506
JAK17.96IC5011nMCHEMBL_ACT_24788524
JAK17.96IC5011nMCHEMBL_ACT_25044274
JAK27.96IC5011nMCHEMBL_ACT_25839852
JAK17.96IC5011nMCHEMBL_ACT_25848313
JAK17.96IC5011nMCHEMBL_ACT_25905423
JAK17.96IC5011nMCHEMBL_ACT_26008576
JAK17.96IC5011nMCHEMBL_ACT_26309187
JAK17.96IC5011nMCHEMBL_ACT_29231740
JAK27.96IC5011nMCHEMBL_ACT_3227864
JAK17.96IC5011nMCHEMBL_ACT_3227873
JAK27.82IC5015nMCHEMBL_ACT_24849124
JAK27.75IC5018nMCHEMBL_ACT_24788503
JAK17.75IC5018nMCHEMBL_ACT_24849106
JAK27.75IC5018nMCHEMBL_ACT_25044275
JAK27.75IC5018nMCHEMBL_ACT_25848314
JAK27.75IC5018nMCHEMBL_ACT_25905424
JAK27.75IC5018nMCHEMBL_ACT_26008577
JAK27.75IC5018nMCHEMBL_ACT_26309188
JAK27.75IC5018nMCHEMBL_ACT_29231741
JAK27.75IC5018nMCHEMBL_ACT_3227693
BMPR1B7.72Kd19nMCHEMBL_ACT_17796708
JAK37.72Kd19nMCHEMBL_ACT_25839822

Target pathways

Aggregated over 5 target gene(s): ACVR1, JAK1, JAK2, JAK3, TYK2.

Top Reactome pathways

86 total, by targets touching each:

PathwayTargetsGenes
Interleukin-4 and Interleukin-13 signaling4JAK1, JAK2, JAK3, TYK2
Interleukin-20 family signaling4JAK1, JAK2, JAK3, TYK2
Potential therapeutics for SARS4JAK1, JAK2, JAK3, TYK2
Interleukin-6 signaling3JAK1, JAK2, TYK2
MAPK3 (ERK1) activation3JAK1, JAK2, TYK2
MAPK1 (ERK2) activation3JAK1, JAK2, TYK2
Cytokine Signaling in Immune system3JAK1, JAK2, JAK3
Signal Transduction3JAK1, JAK2, JAK3
Disease3JAK1, JAK2, JAK3
Immune System3JAK1, JAK2, JAK3
Signaling by Interleukins3JAK1, JAK2, JAK3
Interleukin-2 family signaling3JAK1, JAK2, JAK3
Interleukin-3, Interleukin-5 and GM-CSF signaling3JAK1, JAK2, JAK3
Infectious disease3JAK1, JAK2, JAK3
RAF/MAP kinase cascade3JAK1, JAK2, JAK3
MAPK family signaling cascades3JAK1, JAK2, JAK3
MAPK1/MAPK3 signaling3JAK1, JAK2, JAK3
IL-6-type cytokine receptor ligand interactions3JAK1, JAK2, TYK2
Interleukin-35 Signalling3JAK1, JAK2, TYK2
Interleukin-12 signaling3JAK1, JAK2, TYK2
Interleukin-27 signaling3JAK1, JAK2, TYK2
Interleukin receptor SHC signaling3JAK1, JAK2, JAK3
Signaling by CSF3 (G-CSF)3JAK1, JAK2, TYK2
SARS-CoV Infections3JAK1, JAK2, JAK3
Inactivation of CSF3 (G-CSF) signaling3JAK1, JAK2, TYK2
Viral Infection Pathways3JAK1, JAK2, JAK3
Activation of STAT3 by cadherin engagement3JAK1, JAK2, TYK2
RAF-independent MAPK1/3 activation2JAK1, JAK2
Interleukin-7 signaling2JAK1, JAK3
Interleukin-12 family signaling2JAK1, JAK2

Dominant GO biological processes

GO termTargets
cell differentiation5
protein phosphorylation5
cell surface receptor signaling pathway via JAK-STAT4
cytokine-mediated signaling pathway4
intracellular signal transduction4
growth hormone receptor signaling pathway via JAK-STAT4
regulation of cell-cell adhesion4
regulation of multicellular organismal process3
type II interferon-mediated signaling pathway3
cellular response to virus3
regulation of receptor signaling pathway via JAK-STAT3
regulation of alpha-beta T cell activation3
positive regulation of cell migration2
positive regulation of transcription by RNA polymerase II2
positive regulation of SMAD protein signal transduction2

Indications & clinical

Indications

8 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
primary myelofibrosis3MONDO:0009692EFO:0002430
neoplasm3MONDO:0005070EFO:0000616
pancreatic ductal adenocarcinoma3MONDO:0005184MONDO:0005184
essential thrombocythemia2MONDO:0005029EFO:0000479
acquired polycythemia vera2MONDO:0009891EFO:0002429
non-small cell lung carcinoma1MONDO:0005233EFO:0003060
myeloid leukemia1MONDO:0004643MONDO:0004643

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
PHASE27
PHASE15
PHASE34
PHASE1/PHASE24
PHASE41
PHASE2/PHASE31
EARLY_PHASE11
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07498205PHASE4NOT_YET_RECRUITINGComparing Momelotinib and Ruxolitinib in People With Untreated Myelofibrosis and Low Blood Cell Counts
NCT07569081PHASE2/PHASE3NOT_YET_RECRUITINGA Study Evaluating the Efficacy and Safety of Momelotinib in Participants With Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
NCT01969838PHASE3COMPLETEDMomelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
NCT02101021PHASE3TERMINATEDGemcitabine and Nab-paclitaxel Combined With Momelotinib in Participants With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
NCT02101268PHASE3COMPLETEDEfficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF
NCT04173494PHASE3COMPLETEDA Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)
NCT04176198PHASE1/PHASE2RECRUITINGA Study of Oral Nuvisertib (TP-3654) in Patients With Myelofibrosis
NCT05980806PHASE2RECRUITINGA Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia
NCT06235801PHASE1/PHASE2RECRUITINGA Phase I/II Study of Gilteritinib and Momelotinib for Patients With Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia
NCT06517875PHASE2RECRUITINGStudy of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
NCT06847867PHASE2RECRUITINGA Study of Momelotinib in Participants With Low-risk Myelodysplastic Syndrome
NCT07098936PHASE2RECRUITINGMomelotinib in VEXAS Syndrome
NCT00935987PHASE1/PHASE2COMPLETEDSafety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)
NCT01236638PHASE2COMPLETEDExtension Study Evaluating the Long Term Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)
NCT01423058PHASE1/PHASE2COMPLETEDSafety Study Evaluating Twice-Daily Administration of Momelotinib in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis
NCT01998828PHASE2TERMINATEDSafety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia
NCT02124746PHASE2COMPLETEDLong-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia
NCT06150157PHASE1RECRUITINGA Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms
NCT07104799PHASE1RECRUITINGMomelotinib During and After HCT in Myelofibrosis
NCT02206763PHASE1TERMINATEDErlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naive Metastatic Non-Small Cell Lung Cancer (NSCLC)
NCT02244489PHASE1TERMINATEDMomelotinib Combined With Capecitabine and Oxaliplatin in Adults With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma
NCT02258607PHASE1TERMINATEDEfficacy and Safety of Momelotinib Combined With Trametinib in Adults With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase
NCT07071155EARLY_PHASE1RECRUITINGMomelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia
NCT05582083Not specifiedNO_LONGER_AVAILABLEManaged Access Program for Momelotinib in Myelofibrosis

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3, TYK2
FEDRATINIBChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3, TYK2
PazopanibChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3, TYK2
RuxolitinibChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3, TYK2
NINTEDANIBChEMBLPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3, TYK2
PACRITINIBChEMBLPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3, TYK2
DOVITINIBChEMBLPhase 3ACVR1, JAK1, JAK2, JAK3, TYK2
LESTAURTINIBChEMBLPhase 3ACVR1, JAK1, JAK2, JAK3, TYK2
AT-9283ChEMBLPhase 2ACVR1, JAK1, JAK2, JAK3, TYK2
R-406ChEMBLPhase 2ACVR1, JAK1, JAK2, JAK3, TYK2
TOZASERTIBChEMBLPhase 2ACVR1, JAK1, JAK2, JAK3, TYK2
AfatinibPubChemApprovedACVR1, JAK1, JAK2, JAK3, TYK2
GefitinibPubChemApprovedACVR1, JAK1, JAK2, JAK3, TYK2
IdelalisibPubChemApprovedACVR1, JAK1, JAK2, JAK3, TYK2
SelumetinibPubChemApprovedACVR1, JAK1, JAK2, JAK3, TYK2
dacomitinibChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK3, TYK2
DEUCRAVACITINIBChEMBL + PubChemPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
EntrectinibChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK2, JAK3
ErlotinibChEMBL + PubChemPhase 4 (approved)ACVR1, JAK2, JAK3, TYK2
RITLECITINIBChEMBL + PubChemPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
ABROCITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
BARICITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
DASATINIBChEMBLPhase 4 (approved)ACVR1, JAK2, JAK3, TYK2
FILGOTINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
MIDOSTAURINChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
PEFICITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
SUNITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
TOFACITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
UPADACITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3, TYK2
ALVOCIDIBChEMBLPhase 3ACVR1, JAK2, JAK3, TYK2
BREPOCITINIBChEMBLPhase 3JAK1, JAK2, JAK3, TYK2
DELGOCITINIBChEMBLPhase 3JAK1, JAK2, JAK3, TYK2
ITACITINIBChEMBLPhase 3JAK1, JAK2, JAK3, TYK2
ATINVICITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
AZD-1480ChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
BMS-911543ChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
CC-401ChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
CENISERTIBChEMBLPhase 2ACVR1, JAK2, JAK3, TYK2
CERDULATINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
DECERNOTINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
GANDOTINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
GOLIDOCITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
GUSACITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
IFIDANCITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
IZENCITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
NEZULCITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
NS-018ChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
OCLACITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
ROPSACITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
SOLCITINIBChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
SU-014813ChEMBLPhase 2JAK1, JAK2, JAK3, TYK2
FostamatinibPubChemApprovedACVR1, JAK1, JAK2, TYK2
TrametinibPubChemApprovedACVR1, JAK1, JAK2, TYK2
IMATINIBChEMBL + PubChemPhase 4 (approved)JAK1, JAK2, TYK2
PonatinibChEMBL + PubChemPhase 4 (approved)ACVR1, JAK1, JAK2
AXITINIBChEMBLPhase 4 (approved)JAK2, JAK3, TYK2
BOSUTINIBChEMBLPhase 4 (approved)JAK2, JAK3, TYK2
CERITINIBChEMBLPhase 4 (approved)JAK1, JAK2, JAK3
ABIVERTINIBChEMBLPhase 3JAK1, JAK2, JAK3
DEFACTINIBChEMBLPhase 3JAK2, JAK3, TYK2

About this page

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

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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot