Details of the Drug Combination

General Information of Drug Combination (ID: DC64XYH)

• Drug Combination Name: Myricetin + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Myricetin (DMTV4L0): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 7.86
  Bliss Independence Score: 7.86
  Loewe Additivity Score: 8.8
  LHighest Single Agent (HSA) Score: 8.8

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Myricetin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Myricetin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[2]

Myricetin Interacts with 21 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Poly(ADP-ribose) glycohydrolase (PARG)	OT10JTIO	PARG_HUMAN	Decreases Activity	[6]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[7]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[7]
Egl nine homolog 1 (EGLN1)	OT5QODDK	EGLN1_HUMAN	Decreases Expression	[7]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[8]
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (PIK3C2B)	OTY2PROB	P3C2B_HUMAN	Decreases Expression	[9]
Tumor protein p73 (TP73)	OT0LUO47	P73_HUMAN	Increases Expression	[10]
E3 ubiquitin-protein ligase listerin (LTN1)	OTIW2HTX	LTN1_HUMAN	Decreases Expression	[9]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Activity	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Activity	[12]
Cytochrome c oxidase subunit 5B, mitochondrial (COX5B)	OTDP94F3	COX5B_HUMAN	Increases Expression	[9]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Activity	[13]
Tyrosine-protein kinase JAK1 (JAK1)	OT0X3D17	JAK1_HUMAN	Affects Binding	[14]
Cofilin-1 (CFL1)	OTT6D5MH	COF1_HUMAN	Increases Expression	[9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[10]
Cyclin-dependent kinase 4 inhibitor C (CDKN2C)	OTCLOV90	CDN2C_HUMAN	Increases Expression	[15]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Cleavage	[16]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[16]
Quinone oxidoreductase PIG3 (TP53I3)	OTSCM68G	QORX_HUMAN	Increases Expression	[10]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Increases Expression	[10]
Serine/threonine-protein kinase 38-like (STK38L)	OTI00JVW	ST38L_HUMAN	Decreases Expression	[9]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[3]
Acute myeloid leukaemia	2A60	Approved	[4]
Adult acute monocytic leukemia	N.A.	Approved	[3]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]

Idarubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[18]

Idarubicin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[19]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[20]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[20]

Idarubicin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[21]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[21]

Idarubicin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[22]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[17]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Idarubicin 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: 7083).
• [5] Potential interactions among myricetin and dietary flavonols through the inhibition of human UDP-glucuronosyltransferase in vitro. Toxicol Lett. 2022 Apr 1;358:40-47. doi: 10.1016/j.toxlet.2022.01.007. Epub 2022 Jan 19.
• [6] The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells. Toxicol Lett. 2010 Feb 1;192(2):119-25.
• [7] Involvement of SIRT1 in hypoxic down-regulation of c-Myc and beta-catenin and hypoxic preconditioning effect of polyphenols. Toxicol Appl Pharmacol. 2012 Mar 1;259(2):210-8.
• [8] 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.
• [9] Potential role of nucleoside diphosphate kinase in myricetin-induced selective apoptosis in colon cancer HCT-15?cells. Food Chem Toxicol. 2018 Jun;116(Pt B):315-322. doi: 10.1016/j.fct.2018.04.053. Epub 2018 Apr 24.
• [10] 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.
• [11] 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.
• [12] Dietary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells. J Nutr. 2007 Oct;137(10):2190-5. doi: 10.1093/jn/137.10.2190.
• [13] The inhibitory effects of flavonoids and antiestrogens on the Glut1 glucose transporter in human erythrocytes. Chem Biol Interact. 2003 Dec 15;146(3):225-35. doi: 10.1016/j.cbi.2003.06.001.
• [14] Myricetin directly targets JAK1 to inhibit cell transformation. Cancer Lett. 2009 Mar 8;275(1):17-26. doi: 10.1016/j.canlet.2008.09.027. Epub 2008 Nov 7.
• [15] 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.
• [16] Mitochondrial-dependent, reactive oxygen species-independent apoptosis by myricetin: roles of protein kinase C, cytochrome c, and caspase cascade. Biochem Pharmacol. 2005 Mar 15;69(6):913-27. doi: 10.1016/j.bcp.2004.12.005.
• [17] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [19] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [20] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [21] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [22] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.