Details of the Drug Combination

General Information of Drug Combination (ID: DC7S6PH)

Drug Combination Name
Berberine Piperaquine
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Berberine   DMC5Q8X Piperaquine   DMT70RC
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: 1.393
Bliss Independence Score: 1.246
Loewe Additivity Score: 1.731
LHighest Single Agent (HSA) Score: 3.925

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 137 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [9]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Activity [9]
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) OTB97VIK IF2B3_HUMAN Decreases Expression [10]
Protein arginine N-methyltransferase 5 (PRMT5) OTF6IGJS ANM5_HUMAN Increases Expression [4]
Telomerase reverse transcriptase (TERT) OT085VVA TERT_HUMAN Decreases Activity [11]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Expression [12]
Histone acetyltransferase type B catalytic subunit (HAT1) OT307KEN HAT1_HUMAN Increases Expression [4]
Lysine-specific demethylase 6B (KDM6B) OTMZVHSG KDM6B_HUMAN Increases Expression [4]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Affects Binding [13]
Lysine-specific demethylase 6A (KDM6A) OTZM3MJJ KDM6A_HUMAN Increases Expression [4]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [14]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) OTJKOMXE BNI3L_HUMAN Increases Expression [15]
Lysine-specific histone demethylase 1A (KDM1A) OT85JXS5 KDM1A_HUMAN Increases Expression [4]
Histone H2B type 1-K (H2BC12) OTQ8V0KG H2B1K_HUMAN Decreases Expression [4]
Lysine-specific demethylase 4A (KDM4A) OTDN3EGK KDM4A_HUMAN Increases Expression [4]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [16]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Expression [12]
Histone-lysine N-methyltransferase NSD2 (NSD2) OTQ6SW4R NSD2_HUMAN Decreases Expression [4]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [3]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [17]
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]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [17]
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]
Cathepsin D (CTSD) OTQZ36F3 CATD_HUMAN Decreases Cleavage [15]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Decreases Cleavage [15]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Increases Expression [18]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [19]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [5]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [18]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [20]
Histone H2A type 1 (H2AC11) OTN9P0BO H2A1_HUMAN Decreases Expression [4]
Histone H2B type F-M (H2BW2) OT4X4HHV H2BFM_HUMAN Decreases Expression [4]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [17]
Osteopontin (SPP1) OTJGC23Y OSTP_HUMAN Increases Expression [5]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Decreases Activity [12]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Decreases Expression [20]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Increases Expression [21]
Sucrase-isomaltase, intestinal (SI) OTUP724T SUIS_HUMAN Decreases Expression [22]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Activity [3]
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]
Platelet glycoprotein 4 (CD36) OT5CZWKY CD36_HUMAN Increases Expression [23]
CCAAT/enhancer-binding protein beta (CEBPB) OTM9MQIA CEBPB_HUMAN Increases Expression [23]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Decreases Expression [5]
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Decreases Activity [24]
Histone H2B type 1-O (H2BC17) OT8ED05P H2B1O_HUMAN Decreases Expression [4]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [20]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [20]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Expression [20]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [17]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [4]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Decreases Expression [20]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [3]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [5]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [5]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [20]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [17]
Growth/differentiation factor 5 (GDF5) OTOV8S81 GDF5_HUMAN Decreases Expression [5]
Nicotinamide phosphoribosyltransferase (NAMPT) OTVJR3GL NAMPT_HUMAN Decreases Expression [14]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Increases Expression [5]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [20]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [17]
Transcription factor SOX-9 (SOX9) OTVDJFGN SOX9_HUMAN Decreases Expression [5]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [5]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [18]
Cyclin-dependent kinase inhibitor 1C (CDKN1C) OTASTJ3Q CDN1C_HUMAN Increases Expression [5]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A) OT5QQB5L IDH3A_HUMAN Decreases Expression [25]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [20]
Protein arginine N-methyltransferase 2 (PRMT2) OT63JZCI ANM2_HUMAN Increases Expression [4]
Integrin alpha-1 (ITGA1) OTDITIST ITA1_HUMAN Increases Expression [5]
Histone H2B type 1-D (H2BC5) OTXDTDHN H2B1D_HUMAN Decreases Expression [4]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [26]
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 [20]
Cyclin-dependent kinase 6 (CDK6) OTR95N0X CDK6_HUMAN Decreases Expression [20]
Collagen alpha-1(X) chain (COL10A1) OTC4G2YC COAA1_HUMAN Increases Expression [5]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [17]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [20]
Histone acetyltransferase p300 (EP300) OTL8QJDX EP300_HUMAN Increases Expression [4]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) OT4SO7J4 BNIP3_HUMAN Increases Expression [15]
TNF receptor-associated factor 1 (TRAF1) OTTLM5RU TRAF1_HUMAN Increases Expression [17]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [15]
Runt-related transcription factor 2 (RUNX2) OT97RQQM RUNX2_HUMAN Increases Expression [5]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [17]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [25]
Histone-lysine N-methyltransferase SETDB1 (SETDB1) OTWVUA1B SETB1_HUMAN Increases Expression [4]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [25]
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 [15]
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-lysine N-methyltransferase SETD7 (SETD7) OTT49OXF SETD7_HUMAN Increases Expression [4]
Histone deacetylase 2 (HDAC2) OTUYVFKN HDAC2_HUMAN Decreases Expression [4]
CREB-binding protein (CREBBP) OTPA4QGM CBP_HUMAN Increases Expression [4]
Proteoglycan 4 (PRG4) OT34NR3N PRG4_HUMAN Decreases 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]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [14]
Aurora kinase B (AURKB) OTIY4VHU AURKB_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 [14]
Histone-lysine N-methyltransferase SETDB2 (SETDB2) OTBVVP9Q SETB2_HUMAN Increases Expression [4]
Protein arginine N-methyltransferase 1 (PRMT1) OTN8GTXW ANM1_HUMAN Decreases 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 deacetylase 8 (HDAC8) OT5L4RYX HDAC8_HUMAN Decreases Expression [4]
Histone-lysine N-methyltransferase SETD2 (SETD2) OTQW463T SETD2_HUMAN Increases Expression [4]
Histone-lysine N-methyltransferase SETD5 (SETD5) OTRPAVEO SETD5_HUMAN Increases Expression [4]
Histone-lysine N-methyltransferase SMYD3 (SMYD3) OT9YR20G SMYD3_HUMAN Affects 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 [14]
Protein arginine N-methyltransferase 7 (PRMT7) OTE73PO1 ANM7_HUMAN Increases Expression [4]
DNA (DNMT3B) OTZ0JCNP DNM3B_HUMAN Decreases Expression [4]
Lysine-specific demethylase 5B (KDM5B) OT5DL94T KDM5B_HUMAN Increases Expression [4]
Histone deacetylase 9 (HDAC9) OTO8O0LF HDAC9_HUMAN Decreases Expression [4]
Aurora kinase C (AURKC) OTJMOW9V AURKC_HUMAN Increases Expression [4]
Histone deacetylase 5 (HDAC5) OTWG387P HDAC5_HUMAN Increases Expression [4]
Long-chain fatty acid transport protein 5 (SLC27A5) OT4OK511 S27A5_HUMAN Decreases Expression [23]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Affects Response To Substance [12]
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⏷ Show the Full List of 137 DOT(s)
Indication(s) of Piperaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Piperaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [2]
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Piperaquine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [27]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [28]
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References

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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.
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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.
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10 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.
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12 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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14 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.
15 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.
16 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.
17 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.
18 Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth. Toxicol Appl Pharmacol. 2013 Nov 1;272(3):787-96. doi: 10.1016/j.taap.2013.08.008. Epub 2013 Aug 15.
19 Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide. BMC Cancer. 2008 Feb 25;8:58. doi: 10.1186/1471-2407-8-58.
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21 Orally administered berberine ameliorates bleomycin-induced pulmonary fibrosis in mice through promoting activation of PPAR- and subsequent expression of HGF in colons. Toxicol Appl Pharmacol. 2018 Mar 15;343:1-15. doi: 10.1016/j.taap.2018.02.001. Epub 2018 Feb 3.
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25 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.
26 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.
27 Eurartesim - European Medicines Agency
28 Open-label crossover study of primaquine and dihydroartemisinin-piperaquine pharmacokinetics in healthy adult thai subjects. Antimicrob Agents Chemother. 2014 Dec;58(12):7340-6.