Details of the Drug Combination

General Information of Drug Combination (ID: DCFTVPW)

• Drug Combination Name: Ginsenoside Rb1 + Diazoxide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ginsenoside Rb1 (DMF70AB): N.A.
  Diazoxide (DML1538): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.23
  Bliss Independence Score: 3.23
  Loewe Additivity Score: 3.79
  LHighest Single Agent (HSA) Score: 3.8

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 Diazoxide

Disease Entry	ICD 11	Status	REF
Congenital hyperinsulinism	5A4Y	Approved	[2]
Hyperinsulinemia	5A4Y	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Hypertensive emergency	BA03	Approved	[2]
Insulinoma	2C10.1	Approved	[2]
Malignant essential hypertension	BA00	Approved	[2]

Diazoxide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Modulator	[16]

Diazoxide Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[17]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[17]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Activity	[18]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Secretion	[17]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[19]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[19]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Increases Expression	[18]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11)	OTPUUELV	KCJ11_HUMAN	Decreases Expression	[20]

References

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• [2] Diazoxide FDA Label
• [3] 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: 2409).
• [4] Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull. 2000 Dec;23(12):1481-5.
• [5] Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol. 1998 Oct;50(10):1155-60.
• [6] Characterization of the ginsenoside-transforming recombinant beta-glucosidase from Actinosynnema mirum and bioconversion of major ginsenosides into minor ginsenosides. Appl Microbiol Biotechnol. 2013 Jan;97(2):649-59.
• [7] Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus. Appl Microbiol Biotechnol. 2017 Jul;101(13):5427-5437.
• [8] Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res. 2013 Mar;69(1):21-31.
• [9] Genus Enhydrobacter Staley et al. 1987 should be recognized as a member of the family Rhodospirillaceae within the class Alphaproteobacteria. Microbiol Immunol. 2012 Jan;56(1):21-6.
• [10] Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull. 2005 Oct;28(10):1903-8. doi: 10.1248/bpb.28.1903.
• [11] Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells. Toxicol Appl Pharmacol. 2010 Jan 1;242(1):18-28. doi: 10.1016/j.taap.2009.09.009. Epub 2009 Sep 23.
• [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.
• [15] Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol. 2012 Aug 20;25(8):1574-80. doi: 10.1021/tx2005025. Epub 2012 Aug 9.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [17] Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate the production of cytokines by placentas and peripheral blood mononuclear cells in normal pregnancy. J Hypertens. 2006 May;24(5):915-22. doi: 10.1097/01.hjh.0000222762.84605.03.
• [18] Diazoxide-mediated preconditioning against apoptosis involves activation of cAMP-response element-binding protein (CREB) and NFkappaB. J Biol Chem. 2004 Nov 5;279(45):46748-54. doi: 10.1074/jbc.M406217200. Epub 2004 Aug 23.
• [19] Diazoxide-mediated growth inhibition in human lung cancer cells via downregulation of beta-catenin-mediated cyclin D1 transcription. Lung. 2009 Jan-Feb;187(1):61-7. doi: 10.1007/s00408-008-9127-1. Epub 2008 Dec 4.
• [20] Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats. Toxicol Appl Pharmacol. 2013 Feb 1;266(3):375-84. doi: 10.1016/j.taap.2012.11.015. Epub 2012 Nov 28.