General Information of Drug Combination (ID: DCCS77S)

Drug Combination Name
AS-1949490 Teriflunomide
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs AS-1949490   DMZ1OO0 Teriflunomide   DMQ2FKJ
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: 25.19
Bliss Independence Score: 25.19
Loewe Additivity Score: 40.64
LHighest Single Agent (HSA) Score: 40.65

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AS-1949490
Disease Entry ICD 11 Status REF
Non-insulin dependent diabetes 5A11 Investigative [2]
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 [6]
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [3]
Dihydroorotate dehydrogenase (DHODH) TTLVP78 PYRD_HUMAN Modulator [7]
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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 [8]
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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 [9]
Ornithine aminotransferase, mitochondrial (OAT) OTEKO8CT OAT_HUMAN Increases Expression [9]
Heat shock 70 kDa protein 1-like (HSPA1L) OTC2V1K6 HS71L_HUMAN Decreases Expression [9]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [9]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Decreases Expression [9]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) OT4SO7J4 BNIP3_HUMAN Increases Expression [9]
Mitochondrial adenyl nucleotide antiporter SLC25A25 (SLC25A25) OTMNPSNY SCMC2_HUMAN Increases Expression [9]
Mitochondrial fission regulator 2 (MTFR2) OTLOR68D MTFR2_HUMAN Decreases Expression [9]
Choline dehydrogenase, mitochondrial (CHDH) OTO2DPGL CHDH_HUMAN Decreases Expression [9]
Dimethyladenosine transferase 1, mitochondrial (TFB1M) OTFCUSAZ TFB1M_HUMAN Decreases Expression [9]
Probable ATP-dependent RNA helicase DDX28 (DDX28) OTIIHNYN DDX28_HUMAN Decreases Expression [9]
Glucocorticoid receptor (NR3C1) OTCI2YDI GCR_HUMAN Increases Activity [10]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [10]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [10]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [10]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1) OTNWEJ5Y PCKGC_HUMAN Increases Expression [10]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1) OTJ6FM9F G6PC1_HUMAN Increases Expression [10]
Fatty acid synthase (FASN) OTFII9KG FAS_HUMAN Decreases Expression [10]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Expression [10]
Glycophorin-A (GYPA) OTABU4YV GLPA_HUMAN Increases Expression [11]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [12]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [13]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Increases Expression [11]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [13]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [13]
C-X-C chemokine receptor type 1 (CXCR1) OT5512B2 CXCR1_HUMAN Decreases Expression [12]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [13]
M-phase inducer phosphatase 1 (CDC25A) OTSLKKCO MPIP1_HUMAN Decreases Expression [13]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [13]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [11]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Increases Activity [14]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [13]
Interleukin-10 receptor subunit alpha (IL10RA) OTOX3D1D I10R1_HUMAN Increases Expression [12]
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⏷ Show the Full List of 33 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 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
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 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.
7 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
8 MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
9 Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
10 Teriflunomide is an indirect human constitutive androstane receptor (CAR) activator interacting with epidermal growth factor (EGF) signaling. Front Pharmacol. 2018 Oct 11;9:993.
11 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.
12 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.
13 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.
14 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.