Details of the Drug Combination

General Information of Drug Combination (ID: DCHZCKO)

Drug Combination Name
Arfolitixorin Meclofenamic acid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Arfolitixorin   DMIXMYK Meclofenamic acid   DM05FXR
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 9
Bliss Independence Score: 9
Loewe Additivity Score: 10.63
LHighest Single Agent (HSA) Score: 10.63

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Arfolitixorin
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 3 [2]
Indication(s) of Meclofenamic acid
Disease Entry ICD 11 Status REF
Ankylosing spondylitis FA92.0 Approved [3]
Dysmenorrhea GA34.3 Approved [4]
Joint pain ME82 Approved [3]
Menorrhagia GA20.50 Approved [4]
Osteoarthritis FA00-FA05 Approved [5]
Pain MG30-MG3Z Approved [6]
Meclofenamic acid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Prostaglandin G/H synthase (COX) TTK0943 PGH1_HUMAN; PGH2_HUMAN Inhibitor [7]
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Meclofenamic acid Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [8]
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Meclofenamic acid Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5) OT7FOIK2 LOX5_HUMAN Decreases Activity [9]
Sulfotransferase 1E1 (SULT1E1) OTGPJ517 ST1E1_HUMAN Decreases Activity [10]
Sulfotransferase 1A1 (SULT1A1) OT0K7JIE ST1A1_HUMAN Decreases Activity [10]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [11]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Activity [11]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Decreases Activity [11]
Aldo-keto reductase family 1 member C4 (AKR1C4) OTW2MMOF AK1C4_HUMAN Decreases Activity [12]
L-selectin (SELL) OT6RAJZR LYAM1_HUMAN Decreases Expression [13]
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⏷ Show the Full List of 8 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 ClinicalTrials.gov (NCT03750786) A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer (AGENT). U.S. National Institutes of Health.
3 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: 7219).
4 Use of meclofenamic acid in gynecology and obstetrics: effects on postsurgical stress. Clin J Pain. 1991;7 Suppl 1:S60-3.
5 Quantitation of indomethacin in serum and plasma using gas chromatography-mass spectrometry (GC-MS). Methods Mol Biol. 2010;603:297-305.
6 Meclofenamic Acid Restores Gefinitib Sensitivity by Downregulating Breast Cancer Resistance Protein and Multidrug Resistance Protein 7 via FTO/m6A-Demethylation/c-Myc in Non-Small Cell Lung Cancer. Front Oncol. 2022 Apr 21;12:870636.
7 Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci. 1994 Nov 15;744:50-7.
8 Both reactivity and accessibility are important in cytochrome P450 metabolism: a combined DFT and MD study of fenamic acids in BM3 mutants. J Chem Inf Model. 2019 Feb 25;59(2):743-753.
9 Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro. Prostaglandins Leukot Med. 1986 Aug;23(2-3):229-38.
10 Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents. Curr Drug Metab. 2006 Oct;7(7):745-53.
11 Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs. Chem Biol Interact. 2009 Mar 16;178(1-3):221-7.
12 Initro CAPE inhibitory activity towards human AKR1C3 and the molecular basis. Chem Biol Interact. 2016 Jun 25;253:60-5.
13 Structure-function relationship and role of tumor necrosis factor-alpha-converting enzyme in the down-regulation of L-selectin by non-steroidal anti-inflammatory drugs. J Biol Chem. 2002 Oct 11;277(41):38212-21. doi: 10.1074/jbc.M205142200. Epub 2002 Jul 29.