Details of the Drug Combination

General Information of Drug Combination (ID: DCHZW1T)

• Drug Combination Name: Aloe-emodin + Idarubicin
• Indication: Glioblastoma?; Status: Investigative [1]
• Component Drugs:
  Aloe-emodin (DMPTY8S): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T98G
  Zero Interaction Potency (ZIP) Score: 24.82
  Bliss Independence Score: 24.82
  Loewe Additivity Score: 5.18
  LHighest Single Agent (HSA) Score: 5.18

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Aloe-emodin

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

Aloe-emodin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fatty aldehyde dehydrogenase (ALDH3A2)	TTB6UM0	AL3A2_HUMAN	Inhibitor	[2]

Aloe-emodin Interacts with 29 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Arylamine N-acetyltransferase 1 (NAT1)	OTCCNQ3H	ARY1_HUMAN	Decreases Expression	[7]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[8]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[8]
Sulfotransferase 1E1 (SULT1E1)	OTGPJ517	ST1E1_HUMAN	Decreases Activity	[8]
Sulfotransferase 1A1 (SULT1A1)	OT0K7JIE	ST1A1_HUMAN	Decreases Activity	[8]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[8]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Decreases Activity	[9]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[10]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[5]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[11]
Carbonyl reductase 1 (CBR1)	OTQ3A541	CBR1_HUMAN	Decreases Activity	[9]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Increases Expression	[5]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases Expression	[10]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Increases Expression	[10]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[10]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[11]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[5]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[10]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[10]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[10]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[10]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[10]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[10]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Chemical Synthesis	[12]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Chemical Synthesis	[12]

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	[14]

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	[15]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[16]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[16]

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	[17]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[17]

Idarubicin Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[13]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[18]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[13]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[19]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Activity	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[20]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Decreases Activity	[13]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[21]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[13]

References

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• [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).
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• [7] Effect of inhibition of aloe-emodin on N-acetyltransferase activity and gene expression in human malignant melanoma cells (A375.S2). Melanoma Res. 2005 Dec;15(6):489-94.
• [8] The natural anthraquinones from Rheum palmatum induced the metabolic disorder of melatonin by inhibiting human CYP and SULT enzymes. Toxicol Lett. 2016 Nov 16;262:27-38.
• [9] Inhibition of human carbonyl reducing enzymes by plant anthrone and anthraquinone derivatives. Chem Biol Interact. 2022 Feb 25;354:109823. doi: 10.1016/j.cbi.2022.109823. Epub 2022 Jan 21.
• [10] The molecular effects of aloe-emodin (AE)/liposome-AE on human nonmelanoma skin cancer cells and skin permeation. Chem Res Toxicol. 2009 Dec;22(12):2017-28. doi: 10.1021/tx900318a.
• [11] Anthraquinones inhibit cytochromes P450 enzyme activity in silico and in vitro. J Appl Toxicol. 2021 Sep;41(9):1438-1445. doi: 10.1002/jat.4134. Epub 2021 Jan 12.
• [12] Cytochrome P450 mediated metabolic activation of chrysophanol. Chem Biol Interact. 2018 Jun 1;289:57-67. doi: 10.1016/j.cbi.2018.04.015. Epub 2018 Apr 24.
• [13] 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.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [15] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [16] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [17] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [18] A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
• [19] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
• [20] The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
• [21] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.