Details of the Drug Combination

General Information of Drug Combination (ID: DCB58IY)

Drug Combination Name
Momelotinib Oxaliplatin
Indication
Disease Entry Status REF
Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma Phase 1 [1]
Component Drugs Momelotinib   DMF98Q0 Oxaliplatin   DMQNWRD
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Momelotinib
Disease Entry ICD 11 Status REF
Myelofibrosis 2A20.2 Approved [2]
Polycythemia vera 2A20.4 Phase 2 [3]
Thrombocythemia 3B63 Phase 2 [3]
Momelotinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Janus kinase 2 (JAK-2) TTRMX3V JAK2_HUMAN Modulator [6]
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Momelotinib Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [7]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [7]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [7]
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Momelotinib Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Decreases Phosphorylation [8]
Apoptotic protease-activating factor 1 (APAF1) OTJWIVY0 APAF_HUMAN Increases Expression [8]
Eukaryotic translation initiation factor 4E-binding protein 3 (EIF4EBP3) OTYY2WS5 4EBP3_HUMAN Increases Expression [8]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Decreases Expression [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [8]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Expression [8]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [8]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [8]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [8]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Oxaliplatin
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [4]
Appendiceal neoplasm N.A. Approved [4]
Cholangiocarcinoma 2C12.10 Approved [4]
Colon adenocarcinoma N.A. Approved [4]
Colorectal cancer 2B91.Z Approved [5]
Colorectal carcinoma N.A. Approved [4]
Endocrine gland neoplasm N.A. Approved [4]
Gallbladder carcinoma N.A. Approved [4]
Metastasis from malignant tumor of colon N.A. Approved [4]
Nasopharyngeal carcinoma 2B6B Approved [4]
Peritoneal neoplasm N.A. Approved [4]
Rectal adenocarcinoma 2B92 Approved [4]
Rectal neoplasm N.A. Approved [4]
Rectum mucinous adenocarcinoma N.A. Approved [4]
Colon cancer 2B90.Z Investigative [4]
Gastric cancer 2B72 Investigative [4]
Oxaliplatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [9]
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Oxaliplatin Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [10]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [13]
High affinity copper uptake protein 1 (SLC31A1) DTP8L4F COPT1_HUMAN Substrate [14]
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Oxaliplatin Interacts with 12 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [15]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [15]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [15]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [15]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [16]
Glutathione S-transferase theta-1 (GSTT1) DE3PKUG GSTT1_HUMAN Metabolism [16]
Metallothionein-1A (MT1A) DE5ME8A MT1A_HUMAN Metabolism [16]
Metallothionein-2A (MT2A) DEFKGT7 MT2_HUMAN Metabolism [16]
Myeloperoxidase (MPO) DEA3U9Y PERM_HUMAN Metabolism [16]
Quinone reductase 1 (NQO1) DENP5RY NQO1_HUMAN Metabolism [16]
Superoxide dismutase 1 (SOD1) DEUTDON SODC_HUMAN Metabolism [16]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [16]
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⏷ Show the Full List of 12 DME(s)
Oxaliplatin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Protachykinin-1 (TAC1) OTM842YW TKN1_HUMAN Increases ADR [17]
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References

1 ClinicalTrials.gov (NCT02244489) Momelotinib Combined With Capecitabine and Oxaliplatin in Adults With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma
2 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216873
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Oxaliplatin FDA Label
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7433).
6 Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis.Leukemia.2015 Mar;29(3):741-4.
7 Pharmacokinetics and disposition of momelotinib revealed a disproportionate human metabolite-resolution for clinical development. Drug Metab Dispos. 2018 Mar;46(3):237-247.
8 The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. Biomed Pharmacother. 2016 Aug;82:595-605. doi: 10.1016/j.biopha.2016.05.029. Epub 2016 Jun 9.
9 Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
10 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
11 Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP. Toxicol In Vitro. 2008 Dec;22(8):1846-52.
12 Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
13 Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
14 Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23.
15 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
16 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
17 Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients. Cancer. 2012 Jun 1;118(11):2828-36. doi: 10.1002/cncr.26614. Epub 2011 Oct 21.