Details of the Drug Combination

General Information of Drug Combination (ID: DCV1EXF)

• Drug Combination Name: Aminosalicylic Acid + Ginsenoside Rb1
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Aminosalicylic Acid (DMENSL5): Small molecular drug
  Ginsenoside Rb1 (DMF70AB): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 4.67
  Bliss Independence Score: 4.67
  Loewe Additivity Score: 17.53
  LHighest Single Agent (HSA) Score: 17.55

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Aminosalicylic Acid

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[3]
Pulmonary and extrapulmonary tuberculosis	1B10.Z	Approved	[3]
Pulmonary tuberculosis	1B10.Z	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]

Aminosalicylic Acid Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	TTYZVDJ	DYR_HUMAN	Modulator	[4]
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Modulator	[4]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Modulator	[4]

Aminosalicylic Acid Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Sodium-coupled neutral amino acid transporter 3 (SLC38A3)	DTKWJH3	S38A3_HUMAN	Substrate	[5]

Aminosalicylic Acid Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Metabolism	[6]

Aminosalicylic Acid Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[7]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[7]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[7]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[7]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[7]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[7]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[7]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[7]
Arylamine N-acetyltransferase 1 (NAT1)	OTCCNQ3H	ARY1_HUMAN	Increases Acetylation	[8]

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	[9]
Beta-glucosidase (bglA)	DE4LKZ9	A0A3D1ZWL4_9BIFI	Metabolism	[9]
Beta-glucosidase (bglA)	DEM6GYO	A0A351PC96_9FIRM	Metabolism	[10], [9]
Beta-glucosidase (bglA)	DE9N4OU	C6WCL5_ACTMD	Metabolism	[11]
Beta-glucosidase (bglA)	DERPJZ6	A0A4Q4LS82_BIFAN	Metabolism	[12]
Beta-glucosidase (bglA)	DEVLXCG	R7LVY8_9FUSO	Metabolism	[9]
Beta-glucosidase (bglA)	DEUQTKA	A0A249DCH3_LACRH	Metabolism	[12]
Beta-glucosidase (bglA)	DEXRUS1	A0A267WL33_9BIFI	Metabolism	[13]
Beta-glucosidase (bglA)	DERX7ML	A0A3B8TKP6_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEOHI3U	A0A0P0FEZ9_BACT4	Metabolism	[13]
Beta-glucosidase (bglA)	DE46IH1	A0A1T4QCU7_9PROT	Metabolism	[14]
Beta-glucosidase (bglA)	DEE8WXK	A0A076JJU4_BIFAD	Metabolism	[13]
Beta-glucosidase (bglA)	DECBSVP	A0A126SWK8_9BIFI	Metabolism	[13]
Beta-glucosidase (bglA)	DEAVLU4	BGLFU_BIFBR	Metabolism	[13]
Beta-glucosidase (bglA)	DEPBQES	BGLS_BUTFI	Metabolism	[13]
Beta-glucosidase (bglA)	DEGVUWH	A0A174JG46_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEE8RS0	A0A174GPV4_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEC0M8H	A0A174ZK85_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DE2OMS0	A0A173UNF6_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEPUNVR	A0A395V8H8_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEX7SAW	A0A3R6A2W5_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEE3I1P	A0A412BAD0_9FIRM	Metabolism	[13]
Beta-glucosidase (bglA)	DEASJG5	A5ZMW4_9FIRM	Metabolism	[13]

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	[15]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[16]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases Expression	[17]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[16]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Affects Activity	[18]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[19]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[20]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Aminosalicylic acid FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Identification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2. Biochem J. 2000 May 15;348 Pt 1:159-66.
• [6] Importance of the evaluation of N-acetyltransferase enzyme activity prior to 5-aminosalicylic acid medication for ulcerative colitis. Inflamm Bowel Dis. 2016 Aug;22(8):1793-802.
• [7] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [8] Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.
• [9] Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull. 2000 Dec;23(12):1481-5.
• [10] 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.
• [11] 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.
• [12] Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus. Appl Microbiol Biotechnol. 2017 Jul;101(13):5427-5437.
• [13] Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res. 2013 Mar;69(1):21-31.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.