NAV

Momelotinib

Identification

Summary

Momelotinib is a Janus Kinase inhibitor used to treat intermediate or high-risk myelofibrosis.

Brand Names
Ojjaara
Generic Name
Momelotinib
DrugBank Accession Number
DB11763
Background

Momelotinib is a Janus Kinase 1 (JAK1) and 2 (JAK2) inhibitor. It is a competitive inhibitor of JAK ATP binding.4 First approved by the FDA on September 15, 2023,7 momelotinib is used to treat myelofibrosis.6 Myelofibrosis (MF) is a group of myeloproliferative neoplasms characterized by abnormal proliferative hematopoietic stem cells, leading to the release of cytokines and growth factors. MF includes primary MF (PMF), post-polycythemia vera (PV) MF, and post-essential thrombocythemia (ET) MF. Clinical manifestations of MF include anemia and thrombocytosis. Momelotinib works to block the JAK-signal transducer and activator of transcription (STAT) signalling pathway, which is aberrant in MF.3,4,5

Type
Small Molecule
Groups
Approved, Investigational
Structure
3D
Similar Structures
Weight
Average: 414.469
Monoisotopic: 414.180423972
Chemical Formula
C23H22N6O2
Synonyms
  • Momelotinib
  • N-(CYANOMETHYL)-4-(2-(4-MORPHOLINOANILINO)PYRIMIDIN-4-YL)BENZAMIDE
External IDs
  • CYT-0387
  • CYT-11387
  • CYT-387
  • CYT387
  • GS-0387

Pharmacology

Indication

Momelotinib is indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [postpolycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia.6

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Momelotinib inhibits Janus Kinase 1 and 2 (JAK1/JAK2) with an IC50 of 11 and 18 nM, respectively. It also inhibits JAK3 (IC50 = 155 nM) and tyrosine kinase 2 (TYK2) (IC50 = 17 nM) with less selectivity.3 Momelotinib inhibited STAT3 phosphorylation in whole blood from patients with myelofibrosis (MF). Maximal inhibition of STAT3 phosphorylation occurred two hours after momelotinib dosing, which persisted for at least six hours. Iron availability and erythropoiesis were assessed by analysis of circulating hepcidin concentrations: an acute and sustained reduction of circulating hepcidin was observed for the duration of the 24-week administration of momelotinib to patients with MF.6

Mechanism of action

One of the molecular pathways that have been implicated in the pathogenesis of MF is constitutively activated and dysregulated Janus protein tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) signalling, which is believed to drive the abnormal production of pro-inflammatory cytokines in bone marrow stroma. An aberrant JAK-STAT signalling pathway in MF may or may not be caused by JAK mutations such as JAK2V617F.3,4,5

Momelotinib is an adenosine triphosphate-competitive inhibitor of wild-type JAK1 and JAK2 as well as mutant JAK2V617F, which contribute to the signalling of several 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 other members of the JAK family - 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. Dysregulated JAK signalling may also contribute to inflammation and hyperactivation of ACVR1.6 Suppression of hepcidin by momelotinib increases circulating iron and hemoglobin, and stimulates erythropoiesis in the bone marrow.5

TargetActionsOrganism
ATyrosine-protein kinase JAK1
inhibitor
Humans
ATyrosine-protein kinase JAK2
inhibitor
Humans
UTyrosine-protein kinase JAK3
inhibitor
Humans
UNon-receptor tyrosine-protein kinase TYK2
inhibitor
Humans
UActivin receptor type-1
inhibitor
Humans
UReceptor-type tyrosine-protein kinase FLT3
inhibitor
Humans
Absorption

Momelotinib is rapidly absorbed following oral administration with a bioavailability of 97%.3 The mean (%CV) steady-state Cmax is 479 ng/mL (61%), and the mean (%CV) AUC is 3,288 ng x h/mL (60%) at the maximum recommended dosage. Momelotinib exposure (i.e., Cmax and AUC) increases dose proportionally from 100 mg to 300 mg (0.5 to 1.5 times the maximum recommended dosage), but less than dose-proportional at doses from 400 mg to 800 mg (two to four times the maximum recommended dosage). There is no clinically significant accumulation. The Tmax at steady state is two hours (Q1: 1 hour; Q3: 3 hours) post-dose.6

No clinically significant differences in momelotinib pharmacokinetics were observed following administration of either a high-fat meal (800 kcal; 50% fat) or low-fat meal (400 kcal; 20% fat) in healthy subjects.6

Volume of distribution

The mean (%CV) apparent volume of distribution at steady-state is 984 L (118%).6

Protein binding

Momelotinib is 91% bound to plasma proteins in healthy volunteers.6

Metabolism

Momelotinib is metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP3A4 (36%), CYP2C8 (19%), CYP2C9 (17%), CYP2C19 (19%), and CYP1A2 (9%). M21 is initially formed via oxidation of the morpholine ring by the same CYP enzymes, followed by metabolism via aldehyde oxidase.2,6 M21 is a major metabolite in humans that retains approximately 40% of the pharmacological activity of the parent. The mean ratio of M21 to momelotinib for AUC ranged from 1.4 to 2.1.6 Momelotinib can undergo amide hydrolysis, N-dealkylation, nitrile hydrolysis, nitrile oxidation, and glucuronidation.1

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Route of elimination

Momelotinib is primarily eliminated in feces and, to a lesser extent, in urine. Following a single oral dose of radiolabeled momelotinib in healthy subjects, about 69% of the total radioactive dose was recovered in fecesm with M14 accounting for 21.4% of the dose, momelotinib and M21 each accounting for 13%, and other 12 metabolites accounting for the remaining 22%. About 28% of radioactivity was recovered in urine, with M21 being the major species.2,6

Half-life

The elimination half-life of momelotinib and the M21 metabolite is four to eight hours.6

Clearance

The mean (%CV) clearance is clearance is 103 L/h (87%).6

Adverse Effects
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Toxicity

No information is available regarding the LD50. There is no known antidote for overdose with momelotinib. If an overdose is suspected, the patient should be monitored for signs or symptoms of adverse reactions or effects, and appropriate supportive treatment should be instituted immediately. Further management should be as clinically indicated. Hemodialysis is not expected to enhance the elimination of momelotinib.6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Momelotinib.
AcetylcysteineThe serum concentration of Momelotinib can be increased when it is combined with Acetylcysteine.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Momelotinib.
AllopurinolThe serum concentration of Allopurinol can be increased when it is combined with Momelotinib.
AlpelisibThe serum concentration of Alpelisib can be increased when it is combined with Momelotinib.
Aminohippuric acidThe serum concentration of Momelotinib can be increased when it is combined with Aminohippuric acid.
AmprenavirThe serum concentration of Momelotinib can be increased when it is combined with Amprenavir.
ApalutamideThe serum concentration of Momelotinib can be decreased when it is combined with Apalutamide.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Momelotinib.
AsunaprevirThe serum concentration of Momelotinib can be increased when it is combined with Asunaprevir.
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Food Interactions
  • Take with or without food. Food has no clinically significant effect on drug exposure.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Momelotinib dihydrochlorideRBH995N4961380317-28-1IPNATXQRPWRHKD-UHFFFAOYSA-N
Momelotinib dihydrochloride monohydrateLDX8893L5D1841094-17-4RQKCPSIFARJBOR-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OjjaaraTablet150 mg/1OralGlaxoSmithKline LLC2023-09-15Not applicableUS flag
OjjaaraTablet100 mg/1OralGlaxoSmithKline LLC2023-09-15Not applicableUS flag
OjjaaraTablet200 mg/1OralGlaxoSmithKline LLC2023-09-15Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Phenylpyrimidines
Alternative Parents
Phenylmorpholines / Benzamides / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines / Aminopyrimidines and derivatives / Heteroaromatic compounds / Amino acids and derivatives / Secondary carboxylic acid amides / Dialkyl ethers
show 7 more
Substituents
4-phenylpyrimidine / 5-phenylpyrimidine / Amine / Amino acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Benzamide / Benzenoid
show 26 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
6O01GMS00P
CAS number
1056634-68-4
InChI Key
ZVHNDZWQTBEVRY-UHFFFAOYSA-N
InChI
InChI=1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28)
IUPAC Name
N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide
SMILES
O=C(NCC#N)C1=CC=C(C=C1)C1=CC=NC(NC2=CC=C(C=C2)N2CCOCC2)=N1

References

General References
  1. Zheng J, Xin Y, Zhang J, Subramanian R, Murray BP, Whitney JA, Warr MR, Ling J, Moorehead L, Kwan E, Hemenway J, Smith BJ, Silverman JA: Pharmacokinetics and Disposition of Momelotinib Revealed a Disproportionate Human Metabolite-Resolution for Clinical Development. Drug Metab Dispos. 2018 Mar;46(3):237-247. doi: 10.1124/dmd.117.078899. Epub 2018 Jan 8. [Article]
  2. Xin Y, Kawashima J, Weng W, Kwan E, Tarnowski T, Silverman JA: Pharmacokinetics and Safety of Momelotinib in Subjects With Hepatic or Renal Impairment. J Clin Pharmacol. 2018 Apr;58(4):522-532. doi: 10.1002/jcph.1050. Epub 2017 Dec 28. [Article]
  3. Xu L, Feng J, Gao G, Tang H: Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother. 2019 Nov;20(16):1943-1951. doi: 10.1080/14656566.2019.1657093. Epub 2019 Aug 26. [Article]
  4. Winton EF, Kota V: Momelotinib in myelofibrosis: JAK1/2 inhibitor with a role in treating and understanding the anemia. Future Oncol. 2017 Feb;13(5):395-407. doi: 10.2217/fon-2016-0417. Epub 2016 Oct 27. [Article]
  5. Chifotides HT, Bose P, Verstovsek S: Momelotinib: an emerging treatment for myelofibrosis patients with anemia. J Hematol Oncol. 2022 Jan 19;15(1):7. doi: 10.1186/s13045-021-01157-4. [Article]
  6. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
  7. GSK: Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia [Link]
Human Metabolome Database
HMDB0250717
PubChem Compound
25062766
PubChem Substance
347828117
ChemSpider
24676202
BindingDB
50311017
RxNav
2665204
ChEBI
91407
ChEMBL
CHEMBL1078178
ZINC
ZINC000043199890
PDBe Ligand
C87
Wikipedia
Momelotinib
PDB Entries
6fdz / 7nns

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentPost Polycythemia Vera Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / Primary Myelofibrosis (PMF)3
3TerminatedTreatmentMetastatic Pancreatic Ductal Adenocarcinoma (PDAC)1
2Active Not RecruitingTreatmentNeoplasm / Post Polycythemia Vera Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / Primary Myelofibrosis (PMF)1
2CompletedTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV) / Post Polycythemia Vera Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / Primary Myelofibrosis (PMF)1
2CompletedTreatmentPost Polycythemia Vera Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / Primary Myelofibrosis (PMF)2
2TerminatedTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV)1
1TerminatedTreatmentEGFR Mutated EGFR TKI Naive Metastatic NSCLC1
1TerminatedTreatmentRelapsed Metastatic KRAS-Mutated Non-Small Cell Lung Cancer1
1TerminatedTreatmentRelapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma1
1, 2CompletedTreatmentPost Polycythemia Vera Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / Primary Myelofibrosis (PMF)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral100 mg/1
TabletOral150 mg/1
TabletOral200 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9809559No2015-06-112035-06-11US flag
US8486941No2010-01-032030-01-03US flag
USRE48285No2015-06-112035-06-11US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility<1 mg/mLhttps://www.selleckchem.com/msds/MSDS_S2219.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0325 mg/mLALOGPS
logP2.96ALOGPS
logP2.7Chemaxon
logS-4.1ALOGPS
pKa (Strongest Acidic)14.02Chemaxon
pKa (Strongest Basic)2.62Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area103.17 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity118.46 m3·mol-1Chemaxon
Polarizability44.23 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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insights and accelerate drug research.
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Details1. Tyrosine-protein kinase JAK1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
Gene Name
JAK1
Uniprot ID
P23458
Uniprot Name
Tyrosine-protein kinase JAK1
Molecular Weight
133275.995 Da
References
  1. Xu L, Feng J, Gao G, Tang H: Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother. 2019 Nov;20(16):1943-1951. doi: 10.1080/14656566.2019.1657093. Epub 2019 Aug 26. [Article]
  2. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details2. Tyrosine-protein kinase JAK2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...
Gene Name
JAK2
Uniprot ID
O60674
Uniprot Name
Tyrosine-protein kinase JAK2
Molecular Weight
130672.475 Da
References
  1. Xu L, Feng J, Gao G, Tang H: Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother. 2019 Nov;20(16):1943-1951. doi: 10.1080/14656566.2019.1657093. Epub 2019 Aug 26. [Article]
  2. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details3. Tyrosine-protein kinase JAK3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a...
Gene Name
JAK3
Uniprot ID
P52333
Uniprot Name
Tyrosine-protein kinase JAK3
Molecular Weight
125097.565 Da
References
  1. Xu L, Feng J, Gao G, Tang H: Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother. 2019 Nov;20(16):1943-1951. doi: 10.1080/14656566.2019.1657093. Epub 2019 Aug 26. [Article]
  2. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details4. Non-receptor tyrosine-protein kinase TYK2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.
Gene Name
TYK2
Uniprot ID
P29597
Uniprot Name
Non-receptor tyrosine-protein kinase TYK2
Molecular Weight
133648.77 Da
References
  1. Xu L, Feng J, Gao G, Tang H: Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother. 2019 Nov;20(16):1943-1951. doi: 10.1080/14656566.2019.1657093. Epub 2019 Aug 26. [Article]
  2. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details5. Activin receptor type-1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein serine/threonine kinase activity
Specific Function
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which auto...
Gene Name
ACVR1
Uniprot ID
Q04771
Uniprot Name
Activin receptor type-1
Molecular Weight
57152.41 Da
References
  1. Xu L, Feng J, Gao G, Tang H: Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother. 2019 Nov;20(16):1943-1951. doi: 10.1080/14656566.2019.1657093. Epub 2019 Aug 26. [Article]
  2. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details6. Receptor-type tyrosine-protein kinase FLT3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
References
  1. Azhar M, Kincaid Z, Kesarwani M, Ahmed A, Wunderlich M, Latif T, Starczynowski D, Azam M: Momelotinib is a highly potent inhibitor of FLT3-mutant AML. Blood Adv. 2022 Feb 22;6(4):1186-1192. doi: 10.1182/bloodadvances.2021004611. [Article]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details2. Cytochrome P450 2C8
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details3. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details4. Cytochrome P450 2C19
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details5. Cytochrome P450 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details6. Cytochrome P450 2B6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Momelotinib is a weak, reversible, time-independent inhibitor of CYP2B6.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details7. UDP-glucuronosyltransferase 1-1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
The momelotinib M21 metabolite is an inducer of UGT1A1.
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details8. UDP-glucuronosyltransferase 1-9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]

Transporters

Details1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Momelotinib and M21 are substrates of this transporter in vitro.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details2. ATP-binding cassette sub-family G member 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Momelotinib and M21 are substrates of this transporter in vitro. Momelotinib is an inhibitor of BCRP.
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details3. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Momelotinib and M21 are substrates of this transporter in vitro.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]
Details4. Solute carrier organic anion transporter family member 1B3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Momelotinib and M21 are substrates of this transporter in vitro.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: OJJAARA (momelotinib) tablets, for oral use (September 2023) [Link]

Drug created at October 20, 2016 20:46 / Updated at December 08, 2023 09:53