Details of the Drug Combination

General Information of Drug Combination (ID: DC2VQPG)

Drug Combination Name
Flavonoid derivative 1 Triiodothyronine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Flavonoid derivative 1   DMCQP0B Triiodothyronine   DM14NKM
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: 33.38
Bliss Independence Score: 33.38
Loewe Additivity Score: 46.46
LHighest Single Agent (HSA) Score: 46.46

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Flavonoid derivative 1 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Signal transducer and activator of transcription 3 (STAT3) TTH8FZW STAT3_HUMAN Inhibitor [9]
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Flavonoid derivative 1 Interacts with 76 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [10]
Amine oxidase A (MAOA) OT8NIWMQ AOFA_HUMAN Decreases Activity [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [12]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [13]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [13]
Tumor protein p73 (TP73) OT0LUO47 P73_HUMAN Increases Expression [14]
Prostate stem cell antigen (PSCA) OTQ574EY PSCA_HUMAN Decreases Expression [14]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [14]
CCN family member 5 (CCN5) OTADU8JJ CCN5_HUMAN Decreases Expression [7]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Increases Expression [15]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [16]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Decreases Activity [17]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [15]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Affects Binding [18]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Expression [19]
Catalase (CAT) OTHEBX9R CATA_HUMAN Affects Activity [20]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Expression [21]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [6]
HLA class II histocompatibility antigen gamma chain (CD74) OTO16X4Q HG2A_HUMAN Decreases Expression [22]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [23]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [17]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Expression [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [24]
Fructose-1,6-bisphosphatase 1 (FBP1) OTQBANEP F16P1_HUMAN Decreases Expression [14]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [15]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [25]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [26]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [26]
Pyruvate kinase PKM (PKM) OTLHHMC2 KPYM_HUMAN Increases Activity [27]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [14]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Secretion [28]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [29]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Decreases Activity [17]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Decreases Activity [17]
Early growth response protein 1 (EGR1) OTCP6XGZ EGR1_HUMAN Increases Expression [7]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Decreases Expression [26]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [16]
Nuclear receptor subfamily 1 group D member 1 (NR1D1) OTJ38PTB NR1D1_HUMAN Decreases Expression [7]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Activity [30]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [31]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [31]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [16]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Increases Expression [14]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [32]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [6]
Nitric oxide synthase, inducible (NOS2) OTKKIOJ1 NOS2_HUMAN Decreases Expression [15]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Increases Expression [15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [33]
Cyclin-dependent kinase 4 inhibitor C (CDKN2C) OTCLOV90 CDN2C_HUMAN Decreases Expression [14]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [34]
Mitogen-activated protein kinase 9 (MAPK9) OTCEVJ9E MK09_HUMAN Increases Phosphorylation [34]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [30]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Decreases Expression [16]
Protein FosB (FOSB) OTW6C05J FOSB_HUMAN Decreases Activity [17]
Mitogen-activated protein kinase 10 (MAPK10) OTC46VX1 MK10_HUMAN Increases Phosphorylation [34]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [33]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [34]
Sestrin-2 (SESN2) OT889IXY SESN2_HUMAN Increases Expression [35]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Decreases Phosphorylation [28]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [34]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [34]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [29]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [6]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Activity [36]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Decreases Activity [37]
Quinone oxidoreductase PIG3 (TP53I3) OTSCM68G QORX_HUMAN Increases Expression [14]
Dehydrogenase/reductase SDR family member 11 (DHRS11) OTU3J0ZL DHR11_HUMAN Decreases Activity [38]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Decreases Activity [37]
Estrogen receptor beta (ESR2) OTXNR2WQ ESR2_HUMAN Increases Activity [39]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [6]
Tumor protein 63 (TP63) OT0WOOKQ P63_HUMAN Increases Expression [14]
Serine/threonine-protein kinase TBK1 (TBK1) OT1P06NV TBK1_HUMAN Decreases Activity [40]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Activity [23]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Decreases Activity [41]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Response To Substance [29]
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⏷ Show the Full List of 76 DOT(s)
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]

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 Inhibition of cell growth and VEGF expression in ovarian cancer cells by flavonoids. Nutr Cancer. 2008;60(6):800-9.
5 Structure-dependent modulation of aryl hydrocarbon receptor-mediated activities by flavonoids. Toxicol Sci. 2018 Jul 1;164(1):205-217.
6 Antitumor activity of luteolin in human colon cancer SW620 cells is mediated by the ERK/FOXO3a signaling pathway. Toxicol In Vitro. 2020 Aug;66:104852. doi: 10.1016/j.tiv.2020.104852. Epub 2020 Apr 5.
7 Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro. 2009 Aug;23(5):797-807. doi: 10.1016/j.tiv.2009.04.007. Epub 2009 May 3.
8 Genetic variants of human UGT1A3: functional characterization and frequency distribution in a Chinese Han population. Drug Metab Dispos. 2006 Sep;34(9):1462-7. doi: 10.1124/dmd.106.009761. Epub 2006 May 31.
9 A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
10 Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3. Chem Biol Interact. 2014 Apr 25;213:60-8. doi: 10.1016/j.cbi.2014.02.002. Epub 2014 Feb 11.
11 Evaluation of the inhibitory effects of quercetin-related flavonoids and tea catechins on the monoamine oxidase-A reaction in mouse brain mitochondria. J Agric Food Chem. 2012 Oct 17;60(41):10270-7.
12 Benzo[a]pyrene sensitizes MCF7 breast cancer cells to induction of G1 arrest by the natural flavonoid eupatorin-5-methyl ether, via activation of cell signaling proteins and CYP1-mediated metabolism. Toxicol Lett. 2014 Oct 15;230(2):304-13.
13 Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
14 Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 2008 Jun;46(6):2042-53. doi: 10.1016/j.fct.2008.01.049. Epub 2008 Feb 7.
15 The PPAR-dependent effect of flavonoid luteolin against damage induced by the chemotherapeutic irinotecan in human intestinal cells. Chem Biol Interact. 2022 Jan 5;351:109712. doi: 10.1016/j.cbi.2021.109712. Epub 2021 Oct 23.
16 Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells. Food Chem Toxicol. 2012 Nov;50(11):4136-43. doi: 10.1016/j.fct.2012.08.025. Epub 2012 Aug 20.
17 Luteolin, a flavonoid, inhibits AP-1 activation by basophils. Biochem Biophys Res Commun. 2006 Feb 3;340(1):1-7. doi: 10.1016/j.bbrc.2005.11.157. Epub 2005 Dec 6.
18 Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. doi: 10.1007/s00216-003-2251-0. Epub 2003 Oct 25.
19 The flavonoids apigenin and luteolin suppress ultraviolet A-induced matrix metalloproteinase-1 expression via MAPKs and AP-1-dependent signaling in HaCaT cells. J Dermatol Sci. 2011 Jan;61(1):23-31. doi: 10.1016/j.jdermsci.2010.10.016. Epub 2010 Nov 9.
20 Luteolin as a glycolysis inhibitor offers superior efficacy and lesser toxicity of doxorubicin in breast cancer cells. Biochem Biophys Res Commun. 2008 Aug 1;372(3):497-502. doi: 10.1016/j.bbrc.2008.05.080. Epub 2008 May 27.
21 Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy. 2000 Apr;30(4):501-8. doi: 10.1046/j.1365-2222.2000.00768.x.
22 Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells. J Clin Biochem Nutr. 2008 Sep;43(2):109-17. doi: 10.3164/jcbn.2008054.
23 Luteolin enhances the bioavailability of benzo(a)pyrene in human colon carcinoma cells. Arch Biochem Biophys. 2010 Jun 15;498(2):111-8. doi: 10.1016/j.abb.2010.04.009. Epub 2010 Apr 18.
24 Structure-activity relationship and mechanism of flavonoids on the inhibitory activity of P-glycoprotein (P-gp)-mediated transport of rhodamine123 and daunorubicin in P-gp overexpressed human mouth epidermal carcinoma (KB/MDR) cells. Food Chem Toxicol. 2021 Sep;155:112381. doi: 10.1016/j.fct.2021.112381. Epub 2021 Jul 1.
25 Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res. 2002 May-Jun;22(3):1615-27.
26 Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway. Chem Biol Interact. 2016 Sep 25;257:26-34. doi: 10.1016/j.cbi.2016.07.028. Epub 2016 Jul 26.
27 In vitro effects of some flavones on human pyruvate kinase isoenzyme M2. J Biochem Mol Toxicol. 2015 Mar;29(3):109-13. doi: 10.1002/jbt.21673. Epub 2014 Nov 11.
28 Transinactivation of the epidermal growth factor receptor tyrosine kinase and focal adhesion kinase phosphorylation by dietary flavonoids: effect on invasive potential of human carcinoma cells. Biochem Pharmacol. 2004 Jun 1;67(11):2103-14. doi: 10.1016/j.bcp.2004.02.023.
29 The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells. Toxicol Lett. 2021 Jun 15;344:58-68. doi: 10.1016/j.toxlet.2021.03.006. Epub 2021 Mar 13.
30 Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol. 2001 May 15;61(10):1205-15. doi: 10.1016/s0006-2952(01)00583-4.
31 Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells. Cancer Lett. 2009 Aug 28;281(2):162-70. doi: 10.1016/j.canlet.2009.02.041. Epub 2009 Apr 2.
32 Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2. Biochem Pharmacol. 2005 Feb 15;69(4):699-708. doi: 10.1016/j.bcp.2004.11.002. Epub 2004 Dec 23.
33 Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. Eur J Pharmacol. 2011 Jan 25;651(1-3):18-25. doi: 10.1016/j.ejphar.2010.10.063. Epub 2010 Nov 11.
34 Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicol In Vitro. 2011 Oct;25(7):1385-91. doi: 10.1016/j.tiv.2011.05.009. Epub 2011 May 13.
35 Luteolin prevents liver from tunicamycin-induced endoplasmic reticulum stress via nuclear factor erythroid 2-related factor 2-dependent sestrin 2 induction. Toxicol Appl Pharmacol. 2020 Jul 15;399:115036. doi: 10.1016/j.taap.2020.115036. Epub 2020 May 11.
36 The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF. Antioxid Redox Signal. 2010 Aug 15;13(4):437-48. doi: 10.1089/ars.2009.3000.
37 Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy. Toxicol Sci. 2020 Jun 1;175(2):279-291. doi: 10.1093/toxsci/kfaa033.
38 Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11. Chem Biol Interact. 2019 May 25;305:12-20. doi: 10.1016/j.cbi.2019.03.026. Epub 2019 Mar 26.
39 In vitro estrogenic activity of Achillea millefolium L. Phytomedicine. 2007 Feb;14(2-3):147-52. doi: 10.1016/j.phymed.2006.05.005. Epub 2006 Jul 24.
40 Suppression of the TRIF-dependent signaling pathway of Toll-like receptors by luteolin. Biochem Pharmacol. 2009 Apr 15;77(8):1391-400. doi: 10.1016/j.bcp.2009.01.009. Epub 2009 Jan 23.
41 Drug interaction study of flavonoids toward OATP1B1 and their 3D structure activity relationship analysis for predicting hepatoprotective effects. Toxicology. 2020 May 15;437:152445. doi: 10.1016/j.tox.2020.152445. Epub 2020 Apr 4.