Details of the Drug Combination

General Information of Drug Combination (ID: DCDUYTG)

Drug Combination Name
Berberine Proguanil
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Berberine   DMC5Q8X Proguanil   DMBL79I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 0.998
Bliss Independence Score: 1.383
Loewe Additivity Score: 3.732
LHighest Single Agent (HSA) Score: 7.969

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [6]
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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 [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [8]
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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 [9]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Expression [10]
Histone acetyltransferase type B catalytic subunit (HAT1) OT307KEN HAT1_HUMAN Increases Expression [4]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Affects Binding [11]
Lysine-specific demethylase 6A (KDM6A) OTZM3MJJ KDM6A_HUMAN Increases Expression [4]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [12]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) OTJKOMXE BNI3L_HUMAN Increases Expression [13]
Histone H2B type 1-K (H2BC12) OTQ8V0KG H2B1K_HUMAN Decreases Expression [4]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [14]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Expression [10]
Histone-lysine N-methyltransferase NSD2 (NSD2) OTQ6SW4R NSD2_HUMAN Decreases Expression [4]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Increases Expression [5]
Collagen alpha-1(II) chain (COL2A1) OT5E59C8 CO2A1_HUMAN Decreases Expression [5]
Osteocalcin (BGLAP) OTK1YLWQ OSTCN_HUMAN Increases Expression [5]
Histone H2A type 1-B/E (H2AC4) OTMFQ662 H2A1B_HUMAN Decreases Expression [4]
Histone H2B type 1-J (H2BC11) OTGM083T H2B1J_HUMAN Decreases Expression [4]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [15]
Histone H2A type 1 (H2AC11) OTN9P0BO H2A1_HUMAN Decreases Expression [4]
Histone H2B type F-M (H2BW2) OT4X4HHV H2BFM_HUMAN Decreases Expression [4]
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Decreases Expression [5]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Decreases Expression [4]
Aggrecan core protein (ACAN) OTUOCW8K PGCA_HUMAN Decreases Expression [5]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Decreases Expression [5]
Histone H2B type 1-O (H2BC17) OT8ED05P H2B1O_HUMAN Decreases Expression [4]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [16]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [15]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [15]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Increases Expression [5]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [15]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [16]
Transcription factor SOX-9 (SOX9) OTVDJFGN SOX9_HUMAN Decreases Expression [5]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [5]
Cyclin-dependent kinase inhibitor 1C (CDKN1C) OTASTJ3Q CDN1C_HUMAN Increases Expression [5]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A) OT5QQB5L IDH3A_HUMAN Decreases Expression [17]
Protein arginine N-methyltransferase 2 (PRMT2) OT63JZCI ANM2_HUMAN Increases Expression [4]
Histone H2B type 1-D (H2BC5) OTXDTDHN H2B1D_HUMAN Decreases Expression [4]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [18]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [4]
Histone H2B type 1-C/E/F/G/I (H2BC10) OTLQH0D6 H2B1C_HUMAN Decreases Expression [4]
Histone H3.1 (H3C1) OTGBGOZW H31_HUMAN Decreases Expression [4]
Histone H3.3 (H3-3B) OT9XHQ3C H33_HUMAN Decreases Expression [4]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [15]
Collagen alpha-1(X) chain (COL10A1) OTC4G2YC COAA1_HUMAN Increases Expression [5]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [15]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) OT4SO7J4 BNIP3_HUMAN Increases Expression [13]
TNF receptor-associated factor 1 (TRAF1) OTTLM5RU TRAF1_HUMAN Increases Expression [16]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [17]
Histone-lysine N-methyltransferase SETDB1 (SETDB1) OTWVUA1B SETB1_HUMAN Increases Expression [4]
Histone H3.1t (H3-4) OTY6ITYF H31T_HUMAN Decreases Expression [4]
Histone H2A type 2-A (H2AC18) OTCE5JC7 H2A2A_HUMAN Decreases Expression [4]
Histone H2A type 3 (H2AC25) OTPO62JI H2A3_HUMAN Decreases Expression [4]
Actin-histidine N-methyltransferase (SETD3) OTO5RAU2 SETD3_HUMAN Increases Expression [4]
E3 ubiquitin-protein ligase DZIP3 (DZIP3) OTOFK9KG DZIP3_HUMAN Increases Expression [4]
FUN14 domain-containing protein 1 (FUNDC1) OTA6IVKQ FUND1_HUMAN Increases Expression [13]
Thiosulfate:glutathione sulfurtransferase (TSTD1) OT5DMKFX TSTD1_HUMAN Increases Expression [4]
N-lysine methyltransferase SETD6 (SETD6) OTH5APN1 SETD6_HUMAN Increases Expression [4]
Transcription factor Sp7 (SP7) OT07ETZT SP7_HUMAN Increases Expression [5]
Histone H2A type 1-C (H2AC6) OTF3YK7V H2A1C_HUMAN Decreases Expression [4]
Histone H2B type 1-H (H2BC9) OTQ9XX72 H2B1H_HUMAN Decreases Expression [4]
Histone H2A type 1-H (H2AC12) OTLXVB97 H2A1H_HUMAN Decreases Expression [4]
Protein arginine N-methyltransferase 6 (PRMT6) OT5V3XIN ANM6_HUMAN Increases Expression [4]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [12]
Histone-lysine N-methyltransferase SETDB2 (SETDB2) OTBVVP9Q SETB2_HUMAN Increases Expression [4]
Histone H2B type 1-N (H2BC15) OTU39CFZ H2B1N_HUMAN Decreases Expression [4]
Histone H2A type 1-J (H2AC14) OT5Y4MMC H2A1J_HUMAN Decreases Expression [4]
Histone H2B type 1-M (H2BC14) OTSDZZZY H2B1M_HUMAN Decreases Expression [4]
Histone H2B type 1-L (H2BC13) OTIS8L6R H2B1L_HUMAN Decreases Expression [4]
Osteomodulin (OMD) OTFRELBB OMD_HUMAN Increases Expression [5]
Histone-lysine N-methyltransferase SETD2 (SETD2) OTQW463T SETD2_HUMAN Increases Expression [4]
Histone-lysine N-methyltransferase SETD5 (SETD5) OTRPAVEO SETD5_HUMAN Increases Expression [4]
N-lysine methyltransferase KMT5A (KMT5A) OTW2A5YY KMT5A_HUMAN Increases Expression [4]
Protein arginine N-methyltransferase 8 (PRMT8) OT3MRK62 ANM8_HUMAN Increases Expression [4]
NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) OTMEF544 SIR3_HUMAN Decreases Expression [12]
DNA (DNMT3B) OTZ0JCNP DNM3B_HUMAN Decreases Expression [4]
Long-chain fatty acid transport protein 5 (SLC27A5) OT4OK511 S27A5_HUMAN Decreases Expression [19]
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⏷ Show the Full List of 77 DOT(s)
Indication(s) of Proguanil
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Proguanil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [20]
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Proguanil Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [21]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [22]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [22]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [23]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [24]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hepatoblastoma DCV3LXT HB3 Investigative [25]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
3 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.
4 Berberine acts as a putative epigenetic modulator by affecting the histone code. Toxicol In Vitro. 2016 Oct;36:10-17. doi: 10.1016/j.tiv.2016.06.004. Epub 2016 Jun 13.
5 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.
6 Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine. Parasitol Int. 2002 Mar;51(1):99-103.
7 P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. J Pharm Sci. 2002 Dec;91(12):2614-21.
8 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.
9 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.
10 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.
11 Studies on alkaloids binding to GC-rich human survivin promoter DNA using positive and negative ion electrospray ionization mass spectrometry. J Mass Spectrom. 2008 Mar;43(3):327-35. doi: 10.1002/jms.1320.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
21 In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):747-52.
22 Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol. 1999 Aug;48(2):158-67.
23 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
24 Polymorphic oxidative metabolism of proguanil in a Nigerian population. Eur J Clin Pharmacol. 2002 Nov;58(8):543-5.
25 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976