momelotinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5745 1056634-68-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • momelotinib
  • momelotinib dihydrochloride
  • momelotinib hydrochloride hydrate
  • ojjaara
  • CYT387
  • GS-0387-01
Momelotinib is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2 V617F, which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Momelotinib and its major human circulating metabolite, M21, have higher inhibitory activity for JAK2 compared to JAK3 and tyrosine kinase 2 (TYK2). Momelotinib and M21 additionally inhibit activin A receptor type 1 (ACVR1), also known as activin receptor like kinase 2 (ALK2), which produces subsequent inhibition of liver hepcidin expression and increased iron availability resulting in increased red blood cell production. MF is a myeloproliferative neoplasm associated with constitutive activation and dysregulated JAK signaling that contributes to inflammation and hyperactivation of ACVR1. JAK signaling recruits and activates STAT (signal transducers and activation of transcription) proteins resulting in nuclear localization and subsequent regulation of gene transcription.
  • Molecular weight: 414.47
  • Formula: C23H22N6O2
  • CLOGP: 2.98
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 103.17
  • ALOGS:
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.330 Moderate 0.67
caco2-efflux Caco-2 efflux ratio (BA/AB) 6.166 Moderate 0.67
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 46.881 10^-6 cm/s Moderate 0.67
dh-clint Dog hepatocyte intrinsic clearance 5.420 uL/min/10^6 cells Moderate 0.67
dppb Dog plasma protein binding (% unbound) 11.460 % Moderate 0.67
fcs-ppb Fetal calf serum protein binding (% unbound) 29.040 % Moderate 0.67
herg hERG pIC50 4.622 pIC50 Moderate 0.67
hh-clint Human hepatocyte intrinsic clearance 7.852 uL/min/10^6 cells Moderate 0.67
hlm-clint Human liver microsomal intrinsic clearance 14.421 uL/min/mg protein Moderate 0.67
hppb Human plasma protein binding (% unbound) 9.020 % Moderate 0.67
kinase-safety-class AAK1,ABL1,ABL2,ACVR1B,ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK4,CDK5,CDK6,CDK7,CDK8,CDK9,CHEK1,CHUK,CLK2,CLK4,CSF1R,CSK,CSNK1G2,DDR1,DYRK1A,DYRK1B,DYRK2,DYRK3,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FLT4,FYN,GAK,GRK1,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,IGF1R,IKBKB,INSR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K4,MAP2K6,MAP2K7,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK12,MAPK15,MAPK3,MAPK7,MAPK8,MAPK9,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,MTOR,NTRK1,NTRK2,NTRK3,NUAK1,PAK1,PAK2,PAK4,PAK5,PDGFRB,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CD,PIK3CG,PIM2,PIM3,PRKAA1,PRKAA2,PRKACA,PRKCA,PRKCD,PRKCZ,PRKD1,PRKDC,PTK2,RET,RIPK1,RIPK3,ROCK1,ROCK2,RPS6KA1,SGK1,SIK2,SIK3,SRC,STK10,STK16,STK17A,STK3,STK33,STK4,SYK,TBK1,TEK,TGFBR1,TNIK,TNK1,TTK,TYRO3,UHMK1,ULK1,ULK2,YES1,ZAP70 172
kinase-selectivity-class AAK1,ACVR2A,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2A,CAMK2B,CAMK2D,CDK1,CDK16,CDK2,CDK3,CDK4,CDK6,CDK7,CDK9,CHEK1,CHUK,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,DYRK2,EGFR,EIF2AK3,EPHB4,ERBB2,FGFR1,FLT3,FLT4,FYN,GAK,GRK2,GSK3A,GSK3B,HIPK2,IKBKB,IRAK1,IRAK3,IRAK4,JAK1,JAK2,KDR,KIT,LCK,LRRK2,MAP2K1,MAP2K3,MAP2K6,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K2,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK12,MAPK7,MAPK8,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,NTRK1,NTRK3,NUAK1,PAK4,PDGFRB,PDK1,PDK4,PIK3CA,PIK3CD,PIK3CG,PRKAA1,PRKAA2,PRKCD,ROCK1,ROCK2,SGK1,SIK2,SIK3,SRC,STK16,STK33,SYK,TEK,TGFBR1,TNIK,TNK1,TTK,TYRO3,ULK1,ULK2,YES1 111
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 13.804 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 26.062 Moderate 0.67
mh-clint Mouse hepatocyte intrinsic clearance 33.497 Moderate 0.67
mppb Mouse plasma protein binding (% unbound) 7.980 Moderate 0.67
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 25.293 Moderate 0.67
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 15.220 % Moderate 0.67
rat-kpuu-brain Rat brain Kpuu 0.085 % High 1
rh-clint Rat hepatocyte intrinsic clearance 19.099 uL/min/10^6 cells Moderate 0.67
rh-fuinc Rat hepatocyte fraction unbound in incubation 52.880 % Moderate 0.67
rppb Rat plasma protein binding (% unbound) 4.860 % Moderate 0.67
solubility-dd Solubility at pH 7.4 in DMSO 1.871 uM Moderate 0.67

Approvals:

DateAgencyCompanyOrphan
Sept. 15, 2023 FDA GLAXOSMITHKLINE LLC

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Thrombocytopenia 37.70 37.05 20 255 190259 42430801

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Thrombocytopenia 53.56 40.91 25 345 348860 110240069

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EJ04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Janus-associated kinase (JAK) inhibitors
MeSH PA D000075242 Janus Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:68495 apoptosis inducer
CHEBI has role CHEBI:75835 anti-anaemic agent
CHEBI has role CHEBI:76617 EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

L01EJ Janus-associated kinase (JAK) inhibitors 3 drugs
fedratinibpacritinibruxolitinib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Intermediate or high-risk myelofibrosis indication 52967002 DOID:4971
Primary myelofibrosis indication 307651005
Myelofibrosis due to and following polycythemia vera indication 871540009
Myelofibrosis due to and following essential thrombocythemia indication 871541008




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 8486941 Jan. 3, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 8486941 Jan. 3, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 8486941 Jan. 3, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 9809559 June 11, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL RE48285 June 11, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 9809559 June 11, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL RE48285 June 11, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 9809559 June 11, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL RE48285 June 11, 2035 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 12576089 Aug. 21, 2039 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS IN SUBJECTS HAVING A BASELINE PLATELET COUNT OF AT LEAST 100 BILLION/L BUT LESS THAN 150 BILLION/L AND PREVIOUSLY TREATED WITH A JAK INHIBITOR
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 12576089 Aug. 21, 2039 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS IN SUBJECTS HAVING A BASELINE PLATELET COUNT OF AT LEAST 100 BILLION/L BUT LESS THAN 150 BILLION/L AND PREVIOUSLY TREATED WITH A JAK INHIBITOR
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 12576089 Aug. 21, 2039 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS IN SUBJECTS HAVING A BASELINE PLATELET COUNT OF AT LEAST 100 BILLION/L BUT LESS THAN 150 BILLION/L AND PREVIOUSLY TREATED WITH A JAK INHIBITOR
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 11963962 Dec. 2, 2040 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS IN SUBJECTS HAVING A BASELINE PLATELET COUNT OF LESS THAN 50 BILLION/L
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 11963962 Dec. 2, 2040 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS IN SUBJECTS HAVING A BASELINE PLATELET COUNT OF LESS THAN 50 BILLION/L
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL 11963962 Dec. 2, 2040 FOR THE TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS IN SUBJECTS HAVING A BASELINE PLATELET COUNT OF LESS THAN 50 BILLION/L

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL Sept. 15, 2028 NEW CHEMICAL ENTITY
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL Sept. 15, 2028 NEW CHEMICAL ENTITY
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL Sept. 15, 2028 NEW CHEMICAL ENTITY
EQ 100MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL Sept. 15, 2030 TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS (MF), INCLUDING PRIMARY MF OR SECONDARY MF [POST-POLYCYTHEMIA VERA (PV) AND POST-ESSENTIAL THROMBOCYTHEMIA (ET)], IN ADULTS WITH ANEMIA
EQ 150MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL Sept. 15, 2030 TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS (MF), INCLUDING PRIMARY MF OR SECONDARY MF [POST-POLYCYTHEMIA VERA (PV) AND POST-ESSENTIAL THROMBOCYTHEMIA (ET)], IN ADULTS WITH ANEMIA
EQ 200MG BASE OJJAARA GLAXOSMITHKLINE N216873 Sept. 15, 2023 RX TABLET ORAL Sept. 15, 2030 TREATMENT OF INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS (MF), INCLUDING PRIMARY MF OR SECONDARY MF [POST-POLYCYTHEMIA VERA (PV) AND POST-ESSENTIAL THROMBOCYTHEMIA (ET)], IN ADULTS WITH ANEMIA

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tyrosine-protein kinase JAK1 Kinase INHIBITOR IC50 7.57 DRUG LABEL DRUG LABEL
Tyrosine-protein kinase JAK2 Kinase INHIBITOR IC50 8.85 DRUG LABEL DRUG LABEL
Activin receptor type-1 Kinase INHIBITOR IC50 8.17 DRUG LABEL DRUG LABEL
Rho-associated protein kinase 1 Kinase Kd 5.87 CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.92 CHEMBL
Rho-associated protein kinase 2 Kinase Kd 6.66 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit delta Kinase Kd 6.18 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit gamma Kinase Kd 6.22 CHEMBL
AP2-associated protein kinase 1 Kinase Kd 8.40 CHEMBL
Serine/threonine-protein kinase MARK2 Kinase Kd 6.21 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Kd 6.21 CHEMBL
Serine/threonine-protein kinase 16 Kinase Kd 5.89 CHEMBL
BMP-2-inducible protein kinase Kinase Kd 6.38 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 6.04 CHEMBL
Cyclin-G-associated kinase Kinase Kd 6.08 CHEMBL
Cyclin-dependent kinase 16 Kinase Kd 5.93 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.94 CHEMBL
MAP/microtubule affinity-regulating kinase 3 Kinase Kd 6.38 CHEMBL
Cyclin-dependent kinase 9 Kinase Kd 6.13 CHEMBL
Cyclin-dependent kinase 6 Kinase Kd 5.47 CHEMBL
Cyclin-dependent kinase 17 Kinase Kd 5.86 CHEMBL
Casein kinase II subunit alpha' Kinase Kd 6.52 CHEMBL
Inhibitor of nuclear factor kappa-B kinase subunit epsilon Kinase Kd 6.70 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 6.10 CHEMBL
Citron Rho-interacting kinase Kinase Kd 6.50 CHEMBL
Serine/threonine-protein kinase Nek9 Kinase Kd 6.32 CHEMBL
Serine/threonine-protein kinase D2 Kinase Kd 6.28 CHEMBL
Serine/threonine-protein kinase D3 Kinase Kd 6.19 CHEMBL
Serine/threonine-protein kinase TBK1 Kinase Kd 6.25 CHEMBL
Serine/threonine-protein kinase ICK Kinase Kd 6.14 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 6.54 CHEMBL
Serine/threonine-protein kinase SIK3 Kinase Kd 6.07 CHEMBL
Signal transducer and activator of transcription 3 Transcription factor IC50 5.60 CHEMBL
Serine/threonine-protein kinase Nek3 Kinase Kd 6.54 CHEMBL
Signal transducer and activator of transcription 5A Transcription factor IC50 6.40 CHEMBL
Uncharacterized protein FLJ45252 Unclassified Kd 8.52 CHEMBL
Uncharacterized aarF domain-containing protein kinase 1 Kinase Kd 6.66 CHEMBL
Cyclin-dependent kinase 2 Kinase Kd 5.67 CHEMBL
Tyrosine-protein kinase JAK3 Kinase INHIBITOR IC50 8.21 SCIENTIFIC LITERATURE
Non-receptor tyrosine-protein kinase TYK2 Kinase INHIBITOR IC50 7.70 SCIENTIFIC LITERATURE
Dynamin-like 120 kDa protein, mitochondrial Enzyme Kd 6.15 CHEMBL
Histone deacetylase 1 Enzyme IC50 7.40 CHEMBL
Mitogen-activated protein kinase 8 Kinase Kd 6.22 CHEMBL
Tyrosine-protein kinase JAK2 Kinase IC50 5.82 CHEMBL

External reference:

IDSource
CHEBI:91407 CHEBI
C87 PDB_CHEM_ID
CHEMBL1078178 ChEMBL_ID
C546012 MESH_SUPPLEMENTAL_RECORD_UI
7791 IUPHAR_LIGAND_ID
DB11763 DRUGBANK_ID
1366447007 SNOMEDCT_US
1366449005 SNOMEDCT_US
4042613 VANDF
C2744845 UMLSCUI
CHEMBL2219411 ChEMBL_ID
CHEMBL6068336 ChEMBL_ID
9480 INN_ID
1380317-28-1 SECONDARY_CAS_RN
25062766 PUBCHEM_CID
371325 MMSL
41967 MMSL
d10107 MMSL
019558 NDDF
019559 NDDF
6O01GMS00P UNII
2665204 RXNORM
D10315 KEGG_DRUG
6O01GMS00P INXIGHT DRUGS

Pharmaceutical products:

None