General Information of Drug Combination (ID: DCCGGIF)

Drug Combination Name
Triiodothyronine Efavirenz
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Triiodothyronine   DM14NKM Efavirenz   DMC0GSJ
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: 13.31
Bliss Independence Score: 13.31
Loewe Additivity Score: 31.35
LHighest Single Agent (HSA) Score: 31.36

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Triiodothyronine
Disease Entry ICD 11 Status REF
Euthyroid goiter 5A01.1 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [3]
Indication(s) of Efavirenz
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [4]
Efavirenz Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human immunodeficiency virus Reverse transcriptase (HIV RT) TT84ETX POL_HV1B1 Modulator [5]
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Efavirenz Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [7]
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Efavirenz Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [10]
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Efavirenz Interacts with 32 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [11]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [12]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [12]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [13]
Dynamin-1-like protein (DNM1L) OTXK1Q1G DNM1L_HUMAN Affects Localization [14]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [15]
Dynamin-like 120 kDa protein, mitochondrial (OPA1) OTJGNWPW OPA1_HUMAN Increases Expression [14]
Mitofusin-2 (MFN2) OTPYN8A3 MFN2_HUMAN Increases Expression [14]
Thyroglobulin (TG) OT3ELHIJ THYG_HUMAN Increases Expression [16]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [17]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Secretion [18]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Secretion [18]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [15]
Lipoprotein lipase (LPL) OTTW0267 LIPL_HUMAN Decreases Expression [18]
Thyroid peroxidase (TPO) OTJJLL20 PERT_HUMAN Increases Expression [16]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [18]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [18]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Increases Secretion [18]
Thyrotropin receptor (TSHR) OT0BC8LB TSHR_HUMAN Increases Expression [16]
Calnexin (CANX) OTYP1F6J CALX_HUMAN Affects Localization [14]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [14]
Lon protease homolog, mitochondrial (LONP1) OT665WYT LONM_HUMAN Increases Expression [14]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [18]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [18]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Expression [18]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [15]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [18]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Decreases Expression [18]
Regulator of microtubule dynamics protein 3 (RMDN3) OTKO7AUM RMD3_HUMAN Increases Expression [14]
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) OTQR6ENW M3K5_HUMAN Increases Phosphorylation [15]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [14]
Mitochondrial fission 1 protein (FIS1) OT2HL10J FIS1_HUMAN Increases Expression [14]
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⏷ Show the Full List of 32 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 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076923.
3 ClinicalTrials.gov (NCT04348513) Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection. U.S. National Institutes of Health.
4 Approved antiretroviral drugs. Antiretroviral Drugs. Company report of AVERT. 2009.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
7 Induction of multiple drug transporters by efavirenz. J Pharmacol Sci. 2009 Feb;109(2):242-50.
8 Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol. 2004 Nov;44(11):1273-81.
9 CYP2B6 genotype-dependent inhibition of CYP1A2 and induction of CYP2A6 by the antiretroviral drug efavirenz in healthy volunteers. Clin Transl Sci. 2019 Nov;12(6):657-666.
10 Evaluation of CYP2B6 induction and prediction of clinical drug-drug interactions: considerations from the IQ consortium induction working group-an industry perspective. Drug Metab Dispos. 2016 Oct;44(10):1720-30.
11 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
12 Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol. 2001 Jan;41(1):85-91.
13 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
14 Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress. Br J Pharmacol. 2017 Dec;174(23):4409-4429. doi: 10.1111/bph.14045. Epub 2017 Nov 7.
15 Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes. Toxicol Appl Pharmacol. 2011 Dec 1;257(2):227-34. doi: 10.1016/j.taap.2011.09.008. Epub 2011 Sep 19.
16 Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma. J Clin Endocrinol Metab. 2005 Oct;90(10):5663-71. doi: 10.1210/jc.2005-0367. Epub 2005 Jul 19.
17 Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
18 Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antiviral Res. 2011 Aug;91(2):112-9. doi: 10.1016/j.antiviral.2011.04.018. Epub 2011 May 17.