momelotinib   Click here for help

GtoPdb Ligand ID: 7791

Synonyms: CYT-387 | CYT387 | GS-0387 | GS0387 | Ojjaara® | Omjjara®
Approved drug PDB Ligand
momelotinib is an approved drug (FDA (2023), Japan PMDA & EMA (2024))
Compound class: Synthetic organic
Comment: Momelotinib (a.k.a. CYT387 and GS0387) is an oral Janus kinase inhibitor (ATP-competitive)/activin A receptor type 1 (ACVR1) inhibitor [3]. Inhibition of JAK1/2 is proposed to improve constitutional symptoms (fatigue, night sweats, bone pain) and splenomegaly in myelofibrosis patients. Momelotinib also inhibits the bone morphogenetic protein kinase ACVR1, a mechanism that improves iron homeostasis and erythropoiesis via down-regulation of hepcidin [1], and which may provide benefit to combat anaemia/thrombocytopenia in myelofibrosis [5].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

momelotinib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 103.17
Molecular weight 414.18
XLogP 2.52
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES N#CCNC(=O)c1ccc(cc1)c1ccnc(n1)Nc1ccc(cc1)N1CCOCC1
Isomeric SMILES N#CCNC(=O)c1ccc(cc1)c1ccnc(n1)Nc1ccc(cc1)N1CCOCC1
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)
InChI Key ZVHNDZWQTBEVRY-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Momelotinib reached Phase 3 clinical development for the treatment of primary myelofibrosis (MF), post-polycythemia Vera MF, or post-essential thrombocythemia MF (NCT02101268). Results from the myelofibrosis trial were published in 2018 [2,4].

In September 2023, the FDA approved momelotinib to treat intermediate or high-risk myelofibrosis in adults with anemia.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04173494 A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Patients (MOMENTUM) Phase 3 Interventional Sierra Oncology, Inc.
NCT02101268 Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF Phase 3 Interventional Sierra Oncology, Inc. 2