General Information of Drug Combination (ID: DCUWO91)

Drug Combination Name
NARINGENIN Ursodeoxycholic acid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs NARINGENIN   DMHAZLM Ursodeoxycholic acid   DMCUT21
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 0.36
Bliss Independence Score: 0.36
Loewe Additivity Score: 14.13
LHighest Single Agent (HSA) Score: 14.13

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
NARINGENIN Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [6]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1) TTIWB6L DHB1_HUMAN Inhibitor [7]
Estrogen receptor beta (ESR2) TTOM3J0 ESR2_HUMAN Inhibitor [8]
Lactoylglutathione lyase (GLO1) TTV9A7R LGUL_HUMAN Inhibitor [9]
Cytochrome P450 1B1 (CYP1B1) TTI84H7 CP1B1_HUMAN Inhibitor [10]
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NARINGENIN Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
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NARINGENIN Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 105D7 (cyp105) DECV2ME CYP28_STRAW Metabolism [12]
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Indication(s) of Ursodeoxycholic acid
Disease Entry ICD 11 Status REF
Cholelithiasis DC11 Approved [2]
Primary biliary cholangitis DB96.1 Approved [3]
Primary biliary cirrhosis DB96.1 Approved [4]
Colon cancer 2B90.Z Investigative [5]
Ursodeoxycholic acid Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Solute carrier family 23 member 2 (SLC23A2) TTOP832 S23A2_HUMAN Activator [15]
Biliverdin reductase A (BLVRA) TTJBPN3 BIEA_HUMAN Activator [15]
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Ursodeoxycholic acid Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [16]
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Ursodeoxycholic acid Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Beta-hydroxysteroid dehydrogenase (hdhB) DEOMLHG A4ECA9_9ACTN Metabolism [17]
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Ursodeoxycholic acid Interacts with 104 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Increases Uptake [16]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [18]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Activity [18]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Decreases Activity [18]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [19]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [19]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [20]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [20]
Solute carrier family 23 member 2 (SLC23A2) OTJ5CQMA S23A2_HUMAN Increases Expression [20]
Solute carrier family 23 member 1 (SLC23A1) OTE6F9U6 S23A1_HUMAN Increases Expression [20]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Decreases Expression [21]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [22]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28) OTRBREQ9 ANR28_HUMAN Affects Expression [13]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Increases Expression [23]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Increases Expression [24]
Splicing factor 3B subunit 1 (SF3B1) OTNTX2DG SF3B1_HUMAN Affects Expression [13]
Rho-related BTB domain-containing protein 3 (RHOBTB3) OT1BFKPH RHBT3_HUMAN Affects Expression [13]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Increases Expression [25]
Fibroblast growth factor 19 (FGF19) OT2DVJWY FGF19_HUMAN Increases Expression [23]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) OT7KZMP2 DRA_HUMAN Increases Expression [26]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [27]
Fibrinogen gamma chain (FGG) OT5BJSEX FIBG_HUMAN Affects Expression [13]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Affects Expression [13]
C4b-binding protein alpha chain (C4BPA) OTHNH6Y8 C4BPA_HUMAN Affects Expression [13]
Glucocorticoid receptor (NR3C1) OTCI2YDI GCR_HUMAN Increases Localization [28]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Ubiquitination [29]
ADP/ATP translocase 2 (SLC25A5) OT1XIBMN ADT2_HUMAN Affects Expression [13]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [30]
Large ribosomal subunit protein P2 (RPLP2) OT2YBK3W RLA2_HUMAN Affects Expression [13]
Protein kinase C beta type (PRKCB) OTYQ0656 KPCB_HUMAN Increases Activity [31]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [32]
Involucrin (IVL) OT4VPNGY INVO_HUMAN Decreases Expression [33]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Increases Expression [21]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) OTB8HCED CN37_HUMAN Affects Expression [13]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [22]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [32]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT) OT9LBJVN ODP2_HUMAN Affects Expression [13]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [21]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Affects Expression [13]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [21]
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Decreases Expression [21]
Large ribosomal subunit protein eL33 (RPL35A) OTDDJUWF RL35A_HUMAN Affects Expression [13]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Decreases Expression [21]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Expression [13]
Endothelin-2 (EDN2) OTQ7RCPI EDN2_HUMAN Decreases Expression [34]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [25]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [32]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [21]
Large ribosomal subunit protein uL16 (RPL10) OTBHOZGC RL10_HUMAN Affects Expression [13]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [21]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [32]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [35]
Intercellular adhesion molecule 3 (ICAM3) OTTZ5A5D ICAM3_HUMAN Affects Expression [13]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [21]
Glycine--tRNA ligase (GARS1) OT5B6R9Y GARS_HUMAN Affects Expression [13]
Eukaryotic translation initiation factor 1 (EIF1) OTB4GZ0V EIF1_HUMAN Affects Expression [13]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Increases Expression [35]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [35]
Glutathione synthetase (GSS) OTVSBEIW GSHB_HUMAN Increases Expression [35]
T-complex protein 1 subunit epsilon (CCT5) OTPZ38BT TCPE_HUMAN Affects Expression [13]
Fatty acid synthase (FASN) OTFII9KG FAS_HUMAN Decreases Expression [21]
T-complex protein 1 subunit gamma (CCT3) OTL6EOS1 TCPG_HUMAN Affects Expression [13]
Gastrotropin (FABP6) OTIRQWLW FABP6_HUMAN Increases Expression [36]
Small ribosomal subunit protein mS29 (DAP3) OTNPEZYM RT29_HUMAN Affects Expression [13]
Exportin-2 (CSE1L) OTV2X99A XPO2_HUMAN Affects Expression [13]
Nucleosome assembly protein 1-like 1 (NAP1L1) OTI7WBZV NP1L1_HUMAN Affects Expression [13]
Large ribosomal subunit protein eL27 (RPL27) OTWEOUTX RL27_HUMAN Affects Expression [13]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Activity [37]
Small ribosomal subunit protein uS15 (RPS13) OTOMDIJ2 RS13_HUMAN Affects Expression [13]
Small ribosomal subunit protein eS28 (RPS28) OT12IES1 RS28_HUMAN Affects Expression [13]
Large ribosomal subunit protein eL32 (RPL32) OTKRQJT4 RL32_HUMAN Affects Expression [13]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Affects Expression [13]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Affects Expression [13]
Single-stranded DNA-binding protein, mitochondrial (SSBP1) OTH2PZWH SSBP_HUMAN Affects Expression [13]
Protein kinase C delta type (PRKCD) OTSEH90E KPCD_HUMAN Increases Localization [22]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [32]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [24]
ATP-dependent RNA helicase A (DHX9) OT5AAOQI DHX9_HUMAN Affects Expression [13]
Fibrinogen-like protein 1 (FGL1) OTT0QHQ1 FGL1_HUMAN Affects Expression [13]
Serine/threonine-protein kinase 3 (STK3) OTLNSCQD STK3_HUMAN Affects Expression [13]
DnaJ homolog subfamily C member 3 (DNAJC3) OT7ROIJF DNJC3_HUMAN Decreases Expression [21]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [22]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Localization [35]
Protein Smaug homolog 2 (SAMD4B) OTVRZJ5D SMAG2_HUMAN Affects Expression [13]
Chondroitin sulfate proteoglycan 4 (CSPG4) OTW2D6DE CSPG4_HUMAN Affects Expression [13]
Ribosomal protein eS27-like (RPS27L) OTZWHU0N RS27L_HUMAN Affects Expression [13]
Endoplasmic reticulum metallopeptidase 1 (ERMP1) OT9CIEO2 ERMP1_HUMAN Affects Expression [13]
E3 ubiquitin-protein ligase RBBP6 (RBBP6) OTTVG4HU RBBP6_HUMAN Affects Expression [13]
Out at first protein homolog (OAF) OTOR9CR5 OAF_HUMAN Affects Expression [13]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [23]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [23]
Shieldin complex subunit 2 (SHLD2) OTMLERXL SHLD2_HUMAN Affects Expression [13]
G-protein coupled bile acid receptor 1 (GPBAR1) OT4BKEJ9 GPBAR_HUMAN Decreases Expression [21]
E3 ubiquitin-protein ligase rififylin (RFFL) OT85MGDH RFFL_HUMAN Affects Expression [13]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [38]
AP-2 complex subunit mu (AP2M1) OTQCOSFN AP2M1_HUMAN Affects Expression [13]
Ribosomal protein eL39-like 2 (RPL39L) OTAV1MJQ RL39L_HUMAN Affects Expression [13]
Rho GTPase-activating protein 7 (DLC1) OTP8LMCR RHG07_HUMAN Increases Expression [37]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Expression [21]
Protein sprouty homolog 4 (SPRY4) OT2VK9N0 SPY4_HUMAN Affects Expression [13]
Endosialin (CD248) OTEBWORQ CD248_HUMAN Affects Expression [13]
Soluble lamin-associated protein of 75 kDa (FAM169A) OT2FDMA1 F169A_HUMAN Affects Expression [13]
Sulfotransferase 2A1 (SULT2A1) OT0ISKQ4 ST2A1_HUMAN Increases Sulfation [39]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [16]
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⏷ Show the Full List of 104 DOT(s)

References

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14 UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3. Chem Biol Interact. 2019 Sep 1;310:108745. doi: 10.1016/j.cbi.2019.108745. Epub 2019 Jul 9.
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18 Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003 Feb 1;143-144:503-13.
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20 Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy. Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
21 Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes. PLoS One. 2013 Dec 3;8(12):e82086. doi: 10.1371/journal.pone.0082086. eCollection 2013.
22 Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells. Carcinogenesis. 2011 May;32(5):723-31. doi: 10.1093/carcin/bgr038. Epub 2011 Feb 28.
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24 The synthetic bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide suppresses TNF-induced liver injury. J Hepatol. 2011 Apr;54(4):674-84. doi: 10.1016/j.jhep.2010.07.028. Epub 2010 Sep 27.
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28 Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest. 2008 Feb;118(2):695-709. doi: 10.1172/JCI33156.
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30 Ursodeoxycholic acid inhibits endothelin-1 production in human vascular endothelial cells. Eur J Pharmacol. 2004 Nov 28;505(1-3):67-74. doi: 10.1016/j.ejphar.2004.10.042.
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33 Correlation of chemopreventive efficacy data from the human epidermal cell assay with in vivo data. Anticancer Res. 2000 Jan-Feb;20(1A):27-32.
34 Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis. Aliment Pharmacol Ther. 2005 Feb 1;21(3):227-34. doi: 10.1111/j.1365-2036.2005.02307.x.
35 Ursodeoxycholic acid induces glutathione synthesis through activation of PI3K/Akt pathway in HepG2 cells. Biochem Pharmacol. 2009 Mar 1;77(5):858-66. doi: 10.1016/j.bcp.2008.11.012. Epub 2008 Nov 25.
36 Regulation of ileal bile acid-binding protein expression in Caco-2 cells by ursodeoxycholic acid: role of the farnesoid X receptor. Biochem Pharmacol. 2005 Jun 15;69(12):1755-63. doi: 10.1016/j.bcp.2005.03.019.
37 Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth. Oncol Rep. 2011 Jun;25(6):1739-46. doi: 10.3892/or.2011.1239. Epub 2011 Mar 29.
38 Chemiluminescence quantitative immunohistochemical determination of MRP2 in liver biopsies. J Histochem Cytochem. 2005 Dec;53(12):1451-7. doi: 10.1369/jhc.5A6621.2005. Epub 2005 Jun 13.
39 Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.