Details of the Drug Combination

General Information of Drug Combination (ID: DCDI0VM)

• Drug Combination Name: Ginsenoside Rb1 + Acitretin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ginsenoside Rb1 (DMF70AB): N.A.
  Acitretin (DM8BKU9): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.69
  Bliss Independence Score: 8.69
  Loewe Additivity Score: 17.31
  LHighest Single Agent (HSA) Score: 17.35

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	[3]
Beta-glucosidase (bglA)	DE4LKZ9	A0A3D1ZWL4_9BIFI	Metabolism	[3]
Beta-glucosidase (bglA)	DEM6GYO	A0A351PC96_9FIRM	Metabolism	[4], [3]
Beta-glucosidase (bglA)	DE9N4OU	C6WCL5_ACTMD	Metabolism	[5]
Beta-glucosidase (bglA)	DERPJZ6	A0A4Q4LS82_BIFAN	Metabolism	[6]
Beta-glucosidase (bglA)	DEVLXCG	R7LVY8_9FUSO	Metabolism	[3]
Beta-glucosidase (bglA)	DEUQTKA	A0A249DCH3_LACRH	Metabolism	[6]
Beta-glucosidase (bglA)	DEXRUS1	A0A267WL33_9BIFI	Metabolism	[7]
Beta-glucosidase (bglA)	DERX7ML	A0A3B8TKP6_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEOHI3U	A0A0P0FEZ9_BACT4	Metabolism	[7]
Beta-glucosidase (bglA)	DE46IH1	A0A1T4QCU7_9PROT	Metabolism	[8]
Beta-glucosidase (bglA)	DEE8WXK	A0A076JJU4_BIFAD	Metabolism	[7]
Beta-glucosidase (bglA)	DECBSVP	A0A126SWK8_9BIFI	Metabolism	[7]
Beta-glucosidase (bglA)	DEAVLU4	BGLFU_BIFBR	Metabolism	[7]
Beta-glucosidase (bglA)	DEPBQES	BGLS_BUTFI	Metabolism	[7]
Beta-glucosidase (bglA)	DEGVUWH	A0A174JG46_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEE8RS0	A0A174GPV4_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEC0M8H	A0A174ZK85_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DE2OMS0	A0A173UNF6_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEPUNVR	A0A395V8H8_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEX7SAW	A0A3R6A2W5_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEE3I1P	A0A412BAD0_9FIRM	Metabolism	[7]
Beta-glucosidase (bglA)	DEASJG5	A5ZMW4_9FIRM	Metabolism	[7]

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	[9]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[10]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases Expression	[11]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Affects Activity	[12]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[13]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[14]

Indication(s) of Acitretin

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Approved	[2]

Acitretin 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	[15]

Acitretin Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[16]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Activity	[17]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[18]
Retinoic acid receptor RXR-alpha (RXRA)	OTP1TBDM	RXRA_HUMAN	Affects Binding	[19]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[20]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[17]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[20]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[20]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[21]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[17]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[17]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[18]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Increases Expression	[17]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[17]

References

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• [2] 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: 7598).
• [3] Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull. 2000 Dec;23(12):1481-5.
• [4] 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.
• [5] 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.
• [6] Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus. Appl Microbiol Biotechnol. 2017 Jul;101(13):5427-5437.
• [7] Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res. 2013 Mar;69(1):21-31.
• [8] 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.
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• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
• [16] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [17] Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009 Sep;13(9A):2888-98. doi: 10.1111/j.1582-4934.2008.00397.x. Epub 2009 Jun 20.
• [18] [Effects of all-trans-retinoic acid, acitretin and tazarotene on apoptosis and Bax/Bcl-2 expressions of human melanoma cells A375 and the significance]. Di Yi Jun Yi Da Xue Xue Bao. 2005 Aug;25(8):972-4, 978.
• [19] Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library. Environ Health Perspect. 2019 Sep;127(9):97009. doi: 10.1289/EHP5314. Epub 2019 Sep 30.
• [20] [Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Mar;35(2):182-8. doi: 10.3785/j.issn.1008-9292.2006.02.013.
• [21] Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):393-6. doi: 10.1007/BF02828205.