Details of the Drug Combination

General Information of Drug Combination (ID: DCRDDPW)

• Drug Combination Name: Ginsenoside Rb1 + Idarubicin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ginsenoside Rb1 (DMF70AB): N.A.
  Idarubicin (DMM0XGL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 16.46
  Bliss Independence Score: 16.46
  Loewe Additivity Score: 24.13
  LHighest Single Agent (HSA) Score: 24.15

Molecular Interaction Atlas of This Drug Combination

Ginsenoside Rb1 Interacts with 23 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-glucosidase (bglA)	DEUO7V8	A0A509DD13_9STRE	Metabolism	[4]
Beta-glucosidase (bglA)	DE4LKZ9	A0A3D1ZWL4_9BIFI	Metabolism	[4]
Beta-glucosidase (bglA)	DEM6GYO	A0A351PC96_9FIRM	Metabolism	[5], [4]
Beta-glucosidase (bglA)	DE9N4OU	C6WCL5_ACTMD	Metabolism	[6]
Beta-glucosidase (bglA)	DERPJZ6	A0A4Q4LS82_BIFAN	Metabolism	[7]
Beta-glucosidase (bglA)	DEVLXCG	R7LVY8_9FUSO	Metabolism	[4]
Beta-glucosidase (bglA)	DEUQTKA	A0A249DCH3_LACRH	Metabolism	[7]
Beta-glucosidase (bglA)	DEXRUS1	A0A267WL33_9BIFI	Metabolism	[8]
Beta-glucosidase (bglA)	DERX7ML	A0A3B8TKP6_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEOHI3U	A0A0P0FEZ9_BACT4	Metabolism	[8]
Beta-glucosidase (bglA)	DE46IH1	A0A1T4QCU7_9PROT	Metabolism	[9]
Beta-glucosidase (bglA)	DEE8WXK	A0A076JJU4_BIFAD	Metabolism	[8]
Beta-glucosidase (bglA)	DECBSVP	A0A126SWK8_9BIFI	Metabolism	[8]
Beta-glucosidase (bglA)	DEAVLU4	BGLFU_BIFBR	Metabolism	[8]
Beta-glucosidase (bglA)	DEPBQES	BGLS_BUTFI	Metabolism	[8]
Beta-glucosidase (bglA)	DEGVUWH	A0A174JG46_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEE8RS0	A0A174GPV4_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEC0M8H	A0A174ZK85_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DE2OMS0	A0A173UNF6_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEPUNVR	A0A395V8H8_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEX7SAW	A0A3R6A2W5_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEE3I1P	A0A412BAD0_9FIRM	Metabolism	[8]
Beta-glucosidase (bglA)	DEASJG5	A5ZMW4_9FIRM	Metabolism	[8]

Ginsenoside Rb1 Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Increases Expression	[10]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[11]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases Expression	[12]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Affects Activity	[13]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[14]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[15]

Indication(s) of Idarubicin

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

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	[17]

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	[18]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[19]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[19]

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	[20]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[20]

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	[16]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[21]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[16]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[22]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Activity	[16]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[23]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Decreases Activity	[16]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[24]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[16]

References

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• [2] Idarubicin FDA Label
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• [12] Ginsenosides may enhance the functionality of human embryonic stem cell-derived cardiomyocytes in vitro. Reprod Sci. 2014 Oct;21(10):1312-8. doi: 10.1177/1933719114525269. Epub 2014 Mar 10.
• [13] Modulating effect of ginseng saponins on heterologously expressed HERG currents in Xenopus oocytes. Acta Pharmacol Sin. 2005 May;26(5):551-8. doi: 10.1111/j.1745-7254.2005.00116.x.
• [14] Ginsenoside Rb1 alleviates liver injury induced by 3-chloro-1,2-propanediol by stimulating autophagic flux. J Food Sci. 2021 Dec;86(12):5503-5515. doi: 10.1111/1750-3841.15968. Epub 2021 Nov 23.
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• [16] 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.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [18] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [19] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [20] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [21] 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.
• [22] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
• [23] 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.
• [24] 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.