General Information of Drug Combination (ID: DCW0V6A)

Drug Combination Name
Epinephrine Ursodeoxycholic acid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Epinephrine   DM3KJBC 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: 1.55
Bliss Independence Score: 1.55
Loewe Additivity Score: 2.74
LHighest Single Agent (HSA) Score: 2.74

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Epinephrine
Disease Entry ICD 11 Status REF
Acute asthma CA23 Approved [2]
Allergy 4A80-4A85 Approved [3]
Anaphylaxis N.A. Approved [2]
Bronchiectasis CA24 Approved [2]
Bronchitis CA20 Approved [2]
Periodontitis DA0C Approved [2]
Pulmonary emphysema CA21.Z Approved [2]
Severe asthma CA23 Approved [2]
Asthma CA23 Investigative [2]
Epinephrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Agonist [8]
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Epinephrine Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [9]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [10]
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Epinephrine Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [12]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [13]
Catechol O-methyltransferase (COMT) DEV3T4A COMT_HUMAN Metabolism [14]
Monoamine oxidase type A (MAO-A) DERE4TU AOFA_HUMAN Metabolism [15]
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Epinephrine Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Increases Uptake [16]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [17]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [18]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Activity [19]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Cleavage [20]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Increases Activity [21]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [22]
Alpha-1A adrenergic receptor (ADRA1A) OTUIWCL5 ADA1A_HUMAN Increases Activity [21]
Alpha-1B adrenergic receptor (ADRA1B) OTSAYAFD ADA1B_HUMAN Increases Activity [21]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [22]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases ADR [23]
Equilibrative nucleoside transporter 4 (SLC29A4) OTWTZXMX S29A4_HUMAN Increases Uptake [16]
Alpha-2A adrenergic receptor (ADRA2A) OTZFGOTP ADA2A_HUMAN Increases ADR [23]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Ursodeoxycholic acid
Disease Entry ICD 11 Status REF
Cholelithiasis DC11 Approved [4]
Primary biliary cholangitis DB96.1 Approved [5]
Primary biliary cirrhosis DB96.1 Approved [6]
Colon cancer 2B90.Z Investigative [7]
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 [26]
Biliverdin reductase A (BLVRA) TTJBPN3 BIEA_HUMAN Activator [26]
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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 [27]
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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 [28]
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Ursodeoxycholic acid Interacts with 69 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 [27]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [29]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Activity [29]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Decreases Activity [29]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [30]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [31]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [31]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Decreases Expression [32]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [33]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28) OTRBREQ9 ANR28_HUMAN Affects Expression [24]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Increases Expression [34]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Increases Expression [35]
Splicing factor 3B subunit 1 (SF3B1) OTNTX2DG SF3B1_HUMAN Affects Expression [24]
Rho-related BTB domain-containing protein 3 (RHOBTB3) OT1BFKPH RHBT3_HUMAN Affects Expression [24]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Increases Expression [36]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) OT7KZMP2 DRA_HUMAN Increases Expression [37]
Fibrinogen gamma chain (FGG) OT5BJSEX FIBG_HUMAN Affects Expression [24]
C4b-binding protein alpha chain (C4BPA) OTHNH6Y8 C4BPA_HUMAN Affects Expression [24]
ADP/ATP translocase 2 (SLC25A5) OT1XIBMN ADT2_HUMAN Affects Expression [24]
Large ribosomal subunit protein P2 (RPLP2) OT2YBK3W RLA2_HUMAN Affects Expression [24]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [38]
Involucrin (IVL) OT4VPNGY INVO_HUMAN Decreases Expression [39]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Increases Expression [32]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) OTB8HCED CN37_HUMAN Affects Expression [24]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [33]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT) OT9LBJVN ODP2_HUMAN Affects Expression [24]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [32]
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Decreases Expression [32]
Large ribosomal subunit protein eL33 (RPL35A) OTDDJUWF RL35A_HUMAN Affects Expression [24]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Decreases Expression [32]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Expression [24]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [32]
Large ribosomal subunit protein uL16 (RPL10) OTBHOZGC RL10_HUMAN Affects Expression [24]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [32]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [38]
Intercellular adhesion molecule 3 (ICAM3) OTTZ5A5D ICAM3_HUMAN Affects Expression [24]
Glycine--tRNA ligase (GARS1) OT5B6R9Y GARS_HUMAN Affects Expression [24]
Eukaryotic translation initiation factor 1 (EIF1) OTB4GZ0V EIF1_HUMAN Affects Expression [24]
T-complex protein 1 subunit epsilon (CCT5) OTPZ38BT TCPE_HUMAN Affects Expression [24]
T-complex protein 1 subunit gamma (CCT3) OTL6EOS1 TCPG_HUMAN Affects Expression [24]
Gastrotropin (FABP6) OTIRQWLW FABP6_HUMAN Increases Expression [40]
Small ribosomal subunit protein mS29 (DAP3) OTNPEZYM RT29_HUMAN Affects Expression [24]
Nucleosome assembly protein 1-like 1 (NAP1L1) OTI7WBZV NP1L1_HUMAN Affects Expression [24]
Large ribosomal subunit protein eL27 (RPL27) OTWEOUTX RL27_HUMAN Affects Expression [24]
Small ribosomal subunit protein uS15 (RPS13) OTOMDIJ2 RS13_HUMAN Affects Expression [24]
Small ribosomal subunit protein eS28 (RPS28) OT12IES1 RS28_HUMAN Affects Expression [24]
Large ribosomal subunit protein eL32 (RPL32) OTKRQJT4 RL32_HUMAN Affects Expression [24]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Affects Expression [24]
Single-stranded DNA-binding protein, mitochondrial (SSBP1) OTH2PZWH SSBP_HUMAN Affects Expression [24]
ATP-dependent RNA helicase A (DHX9) OT5AAOQI DHX9_HUMAN Affects Expression [24]
Fibrinogen-like protein 1 (FGL1) OTT0QHQ1 FGL1_HUMAN Affects Expression [24]
Serine/threonine-protein kinase 3 (STK3) OTLNSCQD STK3_HUMAN Affects Expression [24]
DnaJ homolog subfamily C member 3 (DNAJC3) OT7ROIJF DNJC3_HUMAN Decreases Expression [32]
Protein Smaug homolog 2 (SAMD4B) OTVRZJ5D SMAG2_HUMAN Affects Expression [24]
Ribosomal protein eS27-like (RPS27L) OTZWHU0N RS27L_HUMAN Affects Expression [24]
Endoplasmic reticulum metallopeptidase 1 (ERMP1) OT9CIEO2 ERMP1_HUMAN Affects Expression [24]
E3 ubiquitin-protein ligase RBBP6 (RBBP6) OTTVG4HU RBBP6_HUMAN Affects Expression [24]
Out at first protein homolog (OAF) OTOR9CR5 OAF_HUMAN Affects Expression [24]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [34]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [34]
Shieldin complex subunit 2 (SHLD2) OTMLERXL SHLD2_HUMAN Affects Expression [24]
E3 ubiquitin-protein ligase rififylin (RFFL) OT85MGDH RFFL_HUMAN Affects Expression [24]
AP-2 complex subunit mu (AP2M1) OTQCOSFN AP2M1_HUMAN Affects Expression [24]
Ribosomal protein eL39-like 2 (RPL39L) OTAV1MJQ RL39L_HUMAN Affects Expression [24]
Rho GTPase-activating protein 7 (DLC1) OTP8LMCR RHG07_HUMAN Increases Expression [41]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Expression [32]
Protein sprouty homolog 4 (SPRY4) OT2VK9N0 SPY4_HUMAN Affects Expression [24]
Soluble lamin-associated protein of 75 kDa (FAM169A) OT2FDMA1 F169A_HUMAN Affects Expression [24]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [27]
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⏷ Show the Full List of 69 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Epinephrine FDA Label
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 509).
4 Management of symptomatic cholelithiasis: a systematic review. Syst Rev. 2022 Dec 12;11(1):267.
5 Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):93-110.
6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7104).
7 Design and synthesis of bile acid derivatives and their activity against colon cancer. RSC Med Chem. 2022 Aug 19;13(11):1391-1409.
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11 Steroid glucuronides: human circulatory levels and formation by LNCaP cells. J Steroid Biochem Mol Biol. 1991;40(4-6):593-8.
12 Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate. Biochem Biophys Res Commun. 2005 Sep 23;335(2):417-23.
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20 Epinephrine facilitates the growth of T cell lymphoma by altering cell proliferation, apoptosis, and glucose metabolism. Chem Biol Interact. 2023 Jan 5;369:110278. doi: 10.1016/j.cbi.2022.110278. Epub 2022 Nov 22.
21 Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
22 Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway. Cardiovasc Res. 2000 Feb;45(3):788-94. doi: 10.1016/s0008-6363(99)00369-7.
23 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
24 Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
25 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.
26 Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal... Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
27 Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
28 Identification, cloning, heterologous expression, and characterization of a NADPH-dependent 7beta-hydroxysteroid dehydrogenase from Collinsella aerofaciens. Appl Microbiol Biotechnol. 2011 Apr;90(1):127-35.
29 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.
30 Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans. Clin Pharmacol Ther. 2006 May;79(5):449-60.
31 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.
32 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.
33 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.
34 Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.
35 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.
36 The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion. J Biol Chem. 2004 Mar 5;279(10):8856-61. doi: 10.1074/jbc.M306422200. Epub 2003 Dec 18.
37 Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid. Repression of IFN-gamma-induced MHC class II gene expression via a glucocorticoid receptor-dependent pathway. J Immunol. 1996 Feb 15;156(4):1601-8.
38 Mechanism of apoptotic effects induced selectively by ursodeoxycholic acid on human hepatoma cell lines. World J Gastroenterol. 2007 Mar 21;13(11):1652-8. doi: 10.3748/wjg.v13.i11.1652.
39 Correlation of chemopreventive efficacy data from the human epidermal cell assay with in vivo data. Anticancer Res. 2000 Jan-Feb;20(1A):27-32.
40 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.
41 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.