Details of the Drug Combination

General Information of Drug Combination (ID: DCI99KB)

Drug Combination Name
Glatiramer Acetate Teriflunomide
Indication
Disease Entry Status REF
Multiple Sclerosis Phase 1 [1]
Component Drugs Glatiramer Acetate   DMAPV1B Teriflunomide   DMQ2FKJ
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Glatiramer Acetate
Disease Entry ICD 11 Status REF
Multiple sclerosis 8A40 Approved [2]
Glatiramer Acetate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MHC class II antigen DRB1*1 (HLA-DRB1) TTLCMWF 2B11_HUMAN Binder [6]
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Indication(s) of Teriflunomide
Disease Entry ICD 11 Status REF
Hyperlipidaemia 5C80 Approved [3]
Lupus nephritis 4A40.0Y Approved [4]
Multiple sclerosis 8A40 Approved [5]
Psoriatic arthritis FA21 Approved [4]
Rheumatoid arthritis FA20 Phase 3 [5]
Hepatitis B virus infection 1E51.0 Phase 1 [3]
Teriflunomide Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) TT3PQ2Y PYRD_PLAF7 Inhibitor [7]
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [3]
Dihydroorotate dehydrogenase (DHODH) TTLVP78 PYRD_HUMAN Modulator [8]
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Teriflunomide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
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Teriflunomide Interacts with 33 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Phenylalanine--tRNA ligase, mitochondrial (FARS2) OTXAK6F0 SYFM_HUMAN Decreases Expression [10]
Ornithine aminotransferase, mitochondrial (OAT) OTEKO8CT OAT_HUMAN Increases Expression [10]
Heat shock 70 kDa protein 1-like (HSPA1L) OTC2V1K6 HS71L_HUMAN Decreases Expression [10]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [10]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Decreases Expression [10]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) OT4SO7J4 BNIP3_HUMAN Increases Expression [10]
Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25) OTMNPSNY SCMC2_HUMAN Increases Expression [10]
Mitochondrial fission regulator 2 (MTFR2) OTLOR68D MTFR2_HUMAN Decreases Expression [10]
Choline dehydrogenase, mitochondrial (CHDH) OTO2DPGL CHDH_HUMAN Decreases Expression [10]
Dimethyladenosine transferase 1, mitochondrial (TFB1M) OTFCUSAZ TFB1M_HUMAN Decreases Expression [10]
Probable ATP-dependent RNA helicase DDX28 (DDX28) OTIIHNYN DDX28_HUMAN Decreases Expression [10]
Glucocorticoid receptor (NR3C1) OTCI2YDI GCR_HUMAN Increases Activity [11]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [11]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [11]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [11]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1) OTNWEJ5Y PCKGC_HUMAN Increases Expression [11]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1) OTJ6FM9F G6PC1_HUMAN Increases Expression [11]
Fatty acid synthase (FASN) OTFII9KG FAS_HUMAN Decreases Expression [11]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Expression [11]
Glycophorin-A (GYPA) OTABU4YV GLPA_HUMAN Increases Expression [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [13]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [14]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Increases Expression [12]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [14]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [14]
C-X-C chemokine receptor type 1 (CXCR1) OT5512B2 CXCR1_HUMAN Decreases Expression [13]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [14]
M-phase inducer phosphatase 1 (CDC25A) OTSLKKCO MPIP1_HUMAN Decreases Expression [14]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [12]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Increases Activity [15]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [14]
Interleukin-10 receptor subunit alpha (IL10RA) OTOX3D1D I10R1_HUMAN Increases Expression [13]
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⏷ Show the Full List of 33 DOT(s)

References

1 ClinicalTrials.gov (NCT00811395) Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis
2 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: 1058).
3 Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
4 Teriflunomide 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: 6844).
6 Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14593-8.
7 Expression and characterization of E. coli-produced soluble, functional human dihydroorotate dehydrogenase: a potential target for immunosuppression. J Mol Microbiol Biotechnol. 1999 Aug;1(1):183-8.
8 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
9 MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
10 Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
11 Teriflunomide is an indirect human constitutive androstane receptor (CAR) activator interacting with epidermal growth factor (EGF) signaling. Front Pharmacol. 2018 Oct 11;9:993.
12 A77 1726 induces differentiation of human myeloid leukemia K562 cells by depletion of intracellular CTP pools. Mol Pharmacol. 2002 Sep;62(3):463-72. doi: 10.1124/mol.62.3.463.
13 Differential modulation of pro- and anti-inflammatory cytokine receptors by N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of the novel immunomodulator leflunomide. Biochem Pharmacol. 1998 May 1;55(9):1523-9. doi: 10.1016/s0006-2952(97)00677-1.
14 Dihydroorotate dehydrogenase inhibitor A771726 (leflunomide) induces apoptosis and diminishes proliferation of multiple myeloma cells. Mol Cancer Ther. 2009 Feb;8(2):366-75. doi: 10.1158/1535-7163.MCT-08-0664. Epub 2009 Jan 27.
15 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.