Details of the Drug Combination

General Information of Drug Combination (ID: DCKWF9C)

Drug Combination Name
Heparin Ursodeoxycholic acid
Indication
Disease Entry Status REF
Colorectal Cancer Phase 2 [1]
Component Drugs Heparin   DM4ZP3W Ursodeoxycholic acid   DMCUT21
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Heparin
Disease Entry ICD 11 Status REF
Aplastic anemia 3A70 Approved [2]
Bacteremia 1A73 Approved [2]
Burns N.A. Approved [2]
Coronary heart disease BA80.Z Approved [2]
Deep vein thrombosis BD71 Approved [2]
Disseminated intravascular coagulation 3B20 Approved [2]
Metabolic disorder 5C50-5D2Z Approved [2]
Pneumonia CA40 Approved [2]
Pulmonary embolism BB00 Approved [2]
Venous thrombosis BA43 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]
Diabetic angiopathy BD53.Y Investigative [2]
Indication(s) of Ursodeoxycholic acid
Disease Entry ICD 11 Status REF
Cholelithiasis DC11 Approved [5]
Primary biliary cholangitis DB96.1 Approved [6]
Primary biliary cirrhosis DB96.1 Approved [7]
Colon cancer 2B90.Z Investigative [8]
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 [11]
Biliverdin reductase A (BLVRA) TTJBPN3 BIEA_HUMAN Activator [11]
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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 [12]
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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 [13]
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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 [12]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [14]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Activity [14]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Decreases Activity [14]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [15]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [15]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [16]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [16]
Solute carrier family 23 member 2 (SLC23A2) OTJ5CQMA S23A2_HUMAN Increases Expression [16]
Solute carrier family 23 member 1 (SLC23A1) OTE6F9U6 S23A1_HUMAN Increases Expression [16]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Decreases Expression [17]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [18]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28) OTRBREQ9 ANR28_HUMAN Affects Expression [9]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Increases Expression [19]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Increases Expression [20]
Splicing factor 3B subunit 1 (SF3B1) OTNTX2DG SF3B1_HUMAN Affects Expression [9]
Rho-related BTB domain-containing protein 3 (RHOBTB3) OT1BFKPH RHBT3_HUMAN Affects Expression [9]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Increases Expression [21]
Fibroblast growth factor 19 (FGF19) OT2DVJWY FGF19_HUMAN Increases Expression [19]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) OT7KZMP2 DRA_HUMAN Increases Expression [22]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [23]
Fibrinogen gamma chain (FGG) OT5BJSEX FIBG_HUMAN Affects Expression [9]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Affects Expression [9]
C4b-binding protein alpha chain (C4BPA) OTHNH6Y8 C4BPA_HUMAN Affects Expression [9]
Glucocorticoid receptor (NR3C1) OTCI2YDI GCR_HUMAN Increases Localization [24]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Ubiquitination [25]
ADP/ATP translocase 2 (SLC25A5) OT1XIBMN ADT2_HUMAN Affects Expression [9]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [26]
Large ribosomal subunit protein P2 (RPLP2) OT2YBK3W RLA2_HUMAN Affects Expression [9]
Protein kinase C beta type (PRKCB) OTYQ0656 KPCB_HUMAN Increases Activity [27]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [28]
Involucrin (IVL) OT4VPNGY INVO_HUMAN Decreases Expression [29]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Increases Expression [17]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) OTB8HCED CN37_HUMAN Affects Expression [9]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [18]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [28]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT) OT9LBJVN ODP2_HUMAN Affects Expression [9]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [17]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Affects Expression [9]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [17]
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Decreases Expression [17]
Large ribosomal subunit protein eL33 (RPL35A) OTDDJUWF RL35A_HUMAN Affects Expression [9]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Decreases Expression [17]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Expression [9]
Endothelin-2 (EDN2) OTQ7RCPI EDN2_HUMAN Decreases Expression [30]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [21]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [28]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [17]
Large ribosomal subunit protein uL16 (RPL10) OTBHOZGC RL10_HUMAN Affects Expression [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [17]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [28]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [31]
Intercellular adhesion molecule 3 (ICAM3) OTTZ5A5D ICAM3_HUMAN Affects Expression [9]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [17]
Glycine--tRNA ligase (GARS1) OT5B6R9Y GARS_HUMAN Affects Expression [9]
Eukaryotic translation initiation factor 1 (EIF1) OTB4GZ0V EIF1_HUMAN Affects Expression [9]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Increases Expression [31]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [31]
Glutathione synthetase (GSS) OTVSBEIW GSHB_HUMAN Increases Expression [31]
T-complex protein 1 subunit epsilon (CCT5) OTPZ38BT TCPE_HUMAN Affects Expression [9]
Fatty acid synthase (FASN) OTFII9KG FAS_HUMAN Decreases Expression [17]
T-complex protein 1 subunit gamma (CCT3) OTL6EOS1 TCPG_HUMAN Affects Expression [9]
Gastrotropin (FABP6) OTIRQWLW FABP6_HUMAN Increases Expression [32]
Small ribosomal subunit protein mS29 (DAP3) OTNPEZYM RT29_HUMAN Affects Expression [9]
Exportin-2 (CSE1L) OTV2X99A XPO2_HUMAN Affects Expression [9]
Nucleosome assembly protein 1-like 1 (NAP1L1) OTI7WBZV NP1L1_HUMAN Affects Expression [9]
Large ribosomal subunit protein eL27 (RPL27) OTWEOUTX RL27_HUMAN Affects Expression [9]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Activity [33]
Small ribosomal subunit protein uS15 (RPS13) OTOMDIJ2 RS13_HUMAN Affects Expression [9]
Small ribosomal subunit protein eS28 (RPS28) OT12IES1 RS28_HUMAN Affects Expression [9]
Large ribosomal subunit protein eL32 (RPL32) OTKRQJT4 RL32_HUMAN Affects Expression [9]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Affects Expression [9]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Affects Expression [9]
Single-stranded DNA-binding protein, mitochondrial (SSBP1) OTH2PZWH SSBP_HUMAN Affects Expression [9]
Protein kinase C delta type (PRKCD) OTSEH90E KPCD_HUMAN Increases Localization [18]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [28]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [20]
ATP-dependent RNA helicase A (DHX9) OT5AAOQI DHX9_HUMAN Affects Expression [9]
Fibrinogen-like protein 1 (FGL1) OTT0QHQ1 FGL1_HUMAN Affects Expression [9]
Serine/threonine-protein kinase 3 (STK3) OTLNSCQD STK3_HUMAN Affects Expression [9]
DnaJ homolog subfamily C member 3 (DNAJC3) OT7ROIJF DNJC3_HUMAN Decreases Expression [17]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [18]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Localization [31]
Protein Smaug homolog 2 (SAMD4B) OTVRZJ5D SMAG2_HUMAN Affects Expression [9]
Chondroitin sulfate proteoglycan 4 (CSPG4) OTW2D6DE CSPG4_HUMAN Affects Expression [9]
Ribosomal protein eS27-like (RPS27L) OTZWHU0N RS27L_HUMAN Affects Expression [9]
Endoplasmic reticulum metallopeptidase 1 (ERMP1) OT9CIEO2 ERMP1_HUMAN Affects Expression [9]
E3 ubiquitin-protein ligase RBBP6 (RBBP6) OTTVG4HU RBBP6_HUMAN Affects Expression [9]
Out at first protein homolog (OAF) OTOR9CR5 OAF_HUMAN Affects Expression [9]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [19]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [19]
Shieldin complex subunit 2 (SHLD2) OTMLERXL SHLD2_HUMAN Affects Expression [9]
G-protein coupled bile acid receptor 1 (GPBAR1) OT4BKEJ9 GPBAR_HUMAN Decreases Expression [17]
E3 ubiquitin-protein ligase rififylin (RFFL) OT85MGDH RFFL_HUMAN Affects Expression [9]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [34]
AP-2 complex subunit mu (AP2M1) OTQCOSFN AP2M1_HUMAN Affects Expression [9]
Ribosomal protein eL39-like 2 (RPL39L) OTAV1MJQ RL39L_HUMAN Affects Expression [9]
Rho GTPase-activating protein 7 (DLC1) OTP8LMCR RHG07_HUMAN Increases Expression [33]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Expression [17]
Protein sprouty homolog 4 (SPRY4) OT2VK9N0 SPY4_HUMAN Affects Expression [9]
Endosialin (CD248) OTEBWORQ CD248_HUMAN Affects Expression [9]
Soluble lamin-associated protein of 75 kDa (FAM169A) OT2FDMA1 F169A_HUMAN Affects Expression [9]
Sulfotransferase 2A1 (SULT2A1) OT0ISKQ4 ST2A1_HUMAN Increases Sulfation [35]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [12]
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⏷ Show the Full List of 104 DOT(s)

References

1 ClinicalTrials.gov (NCT01149304) Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity
2 Heparin FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 090809.
4 Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec;9(1):727-732.
5 Management of symptomatic cholelithiasis: a systematic review. Syst Rev. 2022 Dec 12;11(1):267.
6 Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):93-110.
7 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).
8 Design and synthesis of bile acid derivatives and their activity against colon cancer. RSC Med Chem. 2022 Aug 19;13(11):1391-1409.
9 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.
10 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.
11 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.
12 Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
13 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.
14 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.
15 Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans. Clin Pharmacol Ther. 2006 May;79(5):449-60.
16 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.
17 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.
18 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.
19 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.
20 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.
21 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.
22 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.
23 Hepatic apolipoprotein A-I gene expression in patients with cholesterol gallstones treated with ursodeoxycholic acid. Ann Hepatol. 2002 Apr-Jun;1(2):85-9.
24 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.
25 Ursodeoxycholic acid modulates the ubiquitin-proteasome degradation pathway of p53. Biochem Biophys Res Commun. 2010 Oct 1;400(4):649-54. doi: 10.1016/j.bbrc.2010.08.121. Epub 2010 Aug 31.
26 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.
27 Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids. Int J Cancer. 1995 Mar 29;61(1):35-9. doi: 10.1002/ijc.2910610107.
28 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.
29 Correlation of chemopreventive efficacy data from the human epidermal cell assay with in vivo data. Anticancer Res. 2000 Jan-Feb;20(1A):27-32.
30 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.
31 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.
32 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.
33 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.
34 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.
35 Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.