Details of the Drug Combination

General Information of Drug Combination (ID: DCEC27D)

Drug Combination Name

Emetine Berberine

Indication

Disease Entry	Status	REF
DD2	Investigative	[1]

Component Drugs

Emetine DMCT2YF

Berberine DMC5Q8X

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: DD2

Zero Interaction Potency (ZIP) Score: 3.315

Bliss Independence Score: 4.829

Loewe Additivity Score: 0.488

LHighest Single Agent (HSA) Score: 1.845

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Emetine

Disease Entry	ICD 11	Status	REF
Hepatitis virus infection	1E50-1E51	Approved	[2]

Emetine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]
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Emetine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[5]
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Emetine Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK)	OT9QIHEQ	RECK_HUMAN	Decreases Expression	[6]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[7]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Decreases Expression	[3]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[3]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Decreases Expression	[3]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Decreases Expression	[3]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[3]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[3]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[6]
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⏷ Show the Full List of 11 DOT(s)

Berberine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Telomerase reverse transcriptase (TERT)	TTUJFD0	TERT_HUMAN	Inhibitor	[12]
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Berberine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[14]
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Berberine Interacts with 77 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)	OTB97VIK	IF2B3_HUMAN	Decreases Expression	[15]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Increases Expression	[16]
Histone acetyltransferase type B catalytic subunit (HAT1)	OT307KEN	HAT1_HUMAN	Increases Expression	[10]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Affects Binding	[17]
Lysine-specific demethylase 6A (KDM6A)	OTZM3MJJ	KDM6A_HUMAN	Increases Expression	[10]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[18]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L)	OTJKOMXE	BNI3L_HUMAN	Increases Expression	[19]
Histone H2B type 1-K (H2BC12)	OTQ8V0KG	H2B1K_HUMAN	Decreases Expression	[10]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[20]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Expression	[16]
Histone-lysine N-methyltransferase NSD2 (NSD2)	OTQ6SW4R	NSD2_HUMAN	Decreases Expression	[10]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[11]
Collagen alpha-1(II) chain (COL2A1)	OT5E59C8	CO2A1_HUMAN	Decreases Expression	[11]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Expression	[11]
Histone H2A type 1-B/E (H2AC4)	OTMFQ662	H2A1B_HUMAN	Decreases Expression	[10]
Histone H2B type 1-J (H2BC11)	OTGM083T	H2B1J_HUMAN	Decreases Expression	[10]
SPARC (SPARC)	OTPN90H0	SPRC_HUMAN	Increases Expression	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[21]
Histone H2A type 1 (H2AC11)	OTN9P0BO	H2A1_HUMAN	Decreases Expression	[10]
Histone H2B type F-M (H2BW2)	OT4X4HHV	H2BFM_HUMAN	Decreases Expression	[10]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Decreases Expression	[11]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Decreases Expression	[10]
Aggrecan core protein (ACAN)	OTUOCW8K	PGCA_HUMAN	Decreases Expression	[11]
Cadherin-2 (CDH2)	OTH0Y56P	CADH2_HUMAN	Decreases Expression	[11]
Histone H2B type 1-O (H2BC17)	OT8ED05P	H2B1O_HUMAN	Decreases Expression	[10]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[22]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[21]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Expression	[11]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[21]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[21]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[22]
Transcription factor SOX-9 (SOX9)	OTVDJFGN	SOX9_HUMAN	Decreases Expression	[11]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase inhibitor 1C (CDKN1C)	OTASTJ3Q	CDN1C_HUMAN	Increases Expression	[11]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A)	OT5QQB5L	IDH3A_HUMAN	Decreases Expression	[23]
Protein arginine N-methyltransferase 2 (PRMT2)	OT63JZCI	ANM2_HUMAN	Increases Expression	[10]
Histone H2B type 1-D (H2BC5)	OTXDTDHN	H2B1D_HUMAN	Decreases Expression	[10]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[24]
Histone H4 (H4C1)	OTB71W46	H4_HUMAN	Decreases Expression	[10]
Histone H2B type 1-C/E/F/G/I (H2BC10)	OTLQH0D6	H2B1C_HUMAN	Decreases Expression	[10]
Histone H3.1 (H3C1)	OTGBGOZW	H31_HUMAN	Decreases Expression	[10]
Histone H3.3 (H3-3B)	OT9XHQ3C	H33_HUMAN	Decreases Expression	[10]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[21]
Collagen alpha-1(X) chain (COL10A1)	OTC4G2YC	COAA1_HUMAN	Increases Expression	[11]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[21]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[19]
TNF receptor-associated factor 1 (TRAF1)	OTTLM5RU	TRAF1_HUMAN	Increases Expression	[22]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[23]
Histone-lysine N-methyltransferase SETDB1 (SETDB1)	OTWVUA1B	SETB1_HUMAN	Increases Expression	[10]
Histone H3.1t (H3-4)	OTY6ITYF	H31T_HUMAN	Decreases Expression	[10]
Histone H2A type 2-A (H2AC18)	OTCE5JC7	H2A2A_HUMAN	Decreases Expression	[10]
Histone H2A type 3 (H2AC25)	OTPO62JI	H2A3_HUMAN	Decreases Expression	[10]
Actin-histidine N-methyltransferase (SETD3)	OTO5RAU2	SETD3_HUMAN	Increases Expression	[10]
E3 ubiquitin-protein ligase DZIP3 (DZIP3)	OTOFK9KG	DZIP3_HUMAN	Increases Expression	[10]
FUN14 domain-containing protein 1 (FUNDC1)	OTA6IVKQ	FUND1_HUMAN	Increases Expression	[19]
Thiosulfate:glutathione sulfurtransferase (TSTD1)	OT5DMKFX	TSTD1_HUMAN	Increases Expression	[10]
N-lysine methyltransferase SETD6 (SETD6)	OTH5APN1	SETD6_HUMAN	Increases Expression	[10]
Transcription factor Sp7 (SP7)	OT07ETZT	SP7_HUMAN	Increases Expression	[11]
Histone H2A type 1-C (H2AC6)	OTF3YK7V	H2A1C_HUMAN	Decreases Expression	[10]
Histone H2B type 1-H (H2BC9)	OTQ9XX72	H2B1H_HUMAN	Decreases Expression	[10]
Histone H2A type 1-H (H2AC12)	OTLXVB97	H2A1H_HUMAN	Decreases Expression	[10]
Protein arginine N-methyltransferase 6 (PRMT6)	OT5V3XIN	ANM6_HUMAN	Increases Expression	[10]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[18]
Histone-lysine N-methyltransferase SETDB2 (SETDB2)	OTBVVP9Q	SETB2_HUMAN	Increases Expression	[10]
Histone H2B type 1-N (H2BC15)	OTU39CFZ	H2B1N_HUMAN	Decreases Expression	[10]
Histone H2A type 1-J (H2AC14)	OT5Y4MMC	H2A1J_HUMAN	Decreases Expression	[10]
Histone H2B type 1-M (H2BC14)	OTSDZZZY	H2B1M_HUMAN	Decreases Expression	[10]
Histone H2B type 1-L (H2BC13)	OTIS8L6R	H2B1L_HUMAN	Decreases Expression	[10]
Osteomodulin (OMD)	OTFRELBB	OMD_HUMAN	Increases Expression	[11]
Histone-lysine N-methyltransferase SETD2 (SETD2)	OTQW463T	SETD2_HUMAN	Increases Expression	[10]
Histone-lysine N-methyltransferase SETD5 (SETD5)	OTRPAVEO	SETD5_HUMAN	Increases Expression	[10]
N-lysine methyltransferase KMT5A (KMT5A)	OTW2A5YY	KMT5A_HUMAN	Increases Expression	[10]
Protein arginine N-methyltransferase 8 (PRMT8)	OT3MRK62	ANM8_HUMAN	Increases Expression	[10]
NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3)	OTMEF544	SIR3_HUMAN	Decreases Expression	[18]
DNA (DNMT3B)	OTZ0JCNP	DNM3B_HUMAN	Decreases Expression	[10]
Long-chain fatty acid transport protein 5 (SLC27A5)	OT4OK511	S27A5_HUMAN	Decreases Expression	[25]
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⏷ Show the Full List of 77 DOT(s)

References

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2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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6	Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
7	Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
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9	Dual down-regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells. Environ Toxicol. 2021 May;36(5):737-747. doi: 10.1002/tox.23076. Epub 2020 Dec 16.
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11	Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/-catenin signaling pathway. Toxicol Lett. 2016 Jan 5;240(1):68-80. doi: 10.1016/j.toxlet.2015.10.007. Epub 2015 Oct 22.
12	Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine. Parasitol Int. 2002 Mar;51(1):99-103.
13	P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. J Pharm Sci. 2002 Dec;91(12):2614-21.
14	Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). Naunyn Schmiedebergs Arch Pharmacol. 2008 Feb;376(6):449-61.
15	Berberine promotes IGF2BP3 ubiquitination by TRIM21 to induce G1/S phase arrest in colorectal cancer cells. Chem Biol Interact. 2023 Apr 1;374:110408. doi: 10.1016/j.cbi.2023.110408. Epub 2023 Feb 21.
16	Mechanism study of goldenseal-associated DNA damage. Toxicol Lett. 2013 Jul 31;221(1):64-72. doi: 10.1016/j.toxlet.2013.05.641. Epub 2013 Jun 5.
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18	Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells. Toxicol Appl Pharmacol. 2016 Jan 15;291:70-83. doi: 10.1016/j.taap.2015.12.006. Epub 2015 Dec 19.
19	Berbamine Hydrochloride inhibits lysosomal acidification by activating Nox2 to potentiate chemotherapy-induced apoptosis via the ROS-MAPK pathway in human lung carcinoma cells. Cell Biol Toxicol. 2023 Aug;39(4):1297-1317. doi: 10.1007/s10565-022-09756-8. Epub 2022 Sep 7.
20	Identification of novel pregnane X receptor activators from traditional Chinese medicines. J Ethnopharmacol. 2011 Jun 14;136(1):137-43. doi: 10.1016/j.jep.2011.04.022. Epub 2011 Apr 16.
21	Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol Cancer Ther. 2006 Feb;5(2):296-308. doi: 10.1158/1535-7163.MCT-05-0448.
22	Cytotoxicity of berberine on human cervical carcinoma HeLa cells through mitochondria, death receptor and MAPK pathways, and in-silico drug-target prediction. Toxicol In Vitro. 2010 Sep;24(6):1482-90. doi: 10.1016/j.tiv.2010.07.017. Epub 2010 Jul 23.
23	Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
24	Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling. Aging (Albany NY). 2012 Dec;4(12):952-65. doi: 10.18632/aging.100521.
25	Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice. Toxicol Appl Pharmacol. 2017 Feb 1;316:74-82. doi: 10.1016/j.taap.2016.12.019. Epub 2016 Dec 28.