Details of the Drug Combination

General Information of Drug Combination (ID: DCR1DUW)

Drug Combination Name
Teriflunomide LY2835219
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Teriflunomide   DMQ2FKJ LY2835219   DM93VBZ
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 6.555
Bliss Independence Score: 16.409
Loewe Additivity Score: 7.049
LHighest Single Agent (HSA) Score: 6.518

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Teriflunomide
Disease Entry ICD 11 Status REF
Hyperlipidaemia 5C80 Approved [2]
Lupus nephritis 4A40.0Y Approved [3]
Multiple sclerosis 8A40 Approved [4]
Psoriatic arthritis FA21 Approved [3]
Rheumatoid arthritis FA20 Phase 3 [4]
Hepatitis B virus infection 1E51.0 Phase 1 [2]
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 [2]
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)
Indication(s) of LY2835219
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [5]
Solid tumour/cancer 2A00-2F9Z Phase 3 [6]
LY2835219 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [17]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [17]
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LY2835219 Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [18]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [18]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [18]
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LY2835219 Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [19]
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LY2835219 Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tripeptidyl-peptidase 1 (TPP1) OT2LQ771 TPP1_HUMAN Increases Expression [16]
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Increases Expression [16]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [16]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Expression [16]
G1/S-specific cyclin-E2 (CCNE2) OTBBUKQQ CCNE2_HUMAN Decreases Expression [20]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases Expression [16]
Fibrinogen beta chain (FGB) OT6RKLI9 FIBB_HUMAN Decreases Expression [16]
Fibrinogen gamma chain (FGG) OT5BJSEX FIBG_HUMAN Decreases Expression [16]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Decreases Expression [16]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [20]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [21]
Gamma-enolase (ENO2) OTRODL0T ENOG_HUMAN Increases Expression [16]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [16]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Affects Expression [22]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [20]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Affects Expression [22]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [22]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Decreases Expression [16]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [16]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Expression [22]
Ephrin-B3 (EFNB3) OT12WTXQ EFNB3_HUMAN Decreases Expression [16]
Insulin growth factor-like family member 2 (IGFL2) OT64M0K7 IGFL2_HUMAN Increases Expression [16]
BRCA1-associated RING domain protein 1 (BARD1) OTTC0Z9Y BARD1_HUMAN Decreases Expression [16]
Fanconi anemia group E protein (FANCE) OTKRPBW1 FANCE_HUMAN Decreases Expression [16]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [21]
Transforming acidic coiled-coil-containing protein 3 (TACC3) OTRNEZTA TACC3_HUMAN Decreases Expression [16]
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⏷ Show the Full List of 27 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 Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
3 Teriflunomide FDA Label
4 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).
5 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
6 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: 7382).
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.
16 Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
17 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
18 Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
19 LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]-Abemaciclib.
20 CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1. J Urol. 2016 Mar;195(3):771-9. doi: 10.1016/j.juro.2015.08.082. Epub 2015 Aug 28.
21 Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42. doi: 10.1016/j.bcp.2016.10.015. Epub 2016 Nov 2.
22 In vitro therapeutic effects of abemaciclib on triple-negative breast cancer cells. J Biochem Mol Toxicol. 2021 Sep;35(9):e22858. doi: 10.1002/jbt.22858. Epub 2021 Jul 26.