Details of the Drug Combination

General Information of Drug Combination (ID: DC6JD46)

Drug Combination Name
BIO-300 Ursodeoxycholic acid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs BIO-300   DMJ7NVI Ursodeoxycholic acid   DMCUT21
N.A. Small molecular drug
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 3.52
Bliss Independence Score: 3.52
Loewe Additivity Score: 3.89
LHighest Single Agent (HSA) Score: 3.89

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of BIO-300
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1/2 [2]
Rheumatoid arthritis FA20 Phase 1 [3]
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 [10]
Biliverdin reductase A (BLVRA) TTJBPN3 BIEA_HUMAN Activator [10]
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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 [11]
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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 [12]
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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 [11]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [13]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Activity [13]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Decreases Activity [13]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [14]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [14]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [15]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [15]
Solute carrier family 23 member 2 (SLC23A2) OTJ5CQMA S23A2_HUMAN Increases Expression [15]
Solute carrier family 23 member 1 (SLC23A1) OTE6F9U6 S23A1_HUMAN Increases Expression [15]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Decreases Expression [16]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [17]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28) OTRBREQ9 ANR28_HUMAN Affects Expression [8]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Increases Expression [18]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Increases Expression [19]
Splicing factor 3B subunit 1 (SF3B1) OTNTX2DG SF3B1_HUMAN Affects Expression [8]
Rho-related BTB domain-containing protein 3 (RHOBTB3) OT1BFKPH RHBT3_HUMAN Affects Expression [8]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Increases Expression [20]
Fibroblast growth factor 19 (FGF19) OT2DVJWY FGF19_HUMAN Increases Expression [18]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) OT7KZMP2 DRA_HUMAN Increases Expression [21]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [22]
Fibrinogen gamma chain (FGG) OT5BJSEX FIBG_HUMAN Affects Expression [8]
Myelin basic protein (MBP) OTFZCEDB MBP_HUMAN Affects Expression [8]
C4b-binding protein alpha chain (C4BPA) OTHNH6Y8 C4BPA_HUMAN Affects Expression [8]
Glucocorticoid receptor (NR3C1) OTCI2YDI GCR_HUMAN Increases Localization [23]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Ubiquitination [24]
ADP/ATP translocase 2 (SLC25A5) OT1XIBMN ADT2_HUMAN Affects Expression [8]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [25]
Large ribosomal subunit protein P2 (RPLP2) OT2YBK3W RLA2_HUMAN Affects Expression [8]
Protein kinase C beta type (PRKCB) OTYQ0656 KPCB_HUMAN Increases Activity [26]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [27]
Involucrin (IVL) OT4VPNGY INVO_HUMAN Decreases Expression [28]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Increases Expression [16]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) OTB8HCED CN37_HUMAN Affects Expression [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [17]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [27]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT) OT9LBJVN ODP2_HUMAN Affects Expression [8]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Decreases Expression [16]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Affects Expression [8]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [16]
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Decreases Expression [16]
Large ribosomal subunit protein eL33 (RPL35A) OTDDJUWF RL35A_HUMAN Affects Expression [8]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Decreases Expression [16]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Expression [8]
Endothelin-2 (EDN2) OTQ7RCPI EDN2_HUMAN Decreases Expression [29]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [20]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [27]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [16]
Large ribosomal subunit protein uL16 (RPL10) OTBHOZGC RL10_HUMAN Affects Expression [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [16]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [27]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [30]
Intercellular adhesion molecule 3 (ICAM3) OTTZ5A5D ICAM3_HUMAN Affects Expression [8]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [16]
Glycine--tRNA ligase (GARS1) OT5B6R9Y GARS_HUMAN Affects Expression [8]
Eukaryotic translation initiation factor 1 (EIF1) OTB4GZ0V EIF1_HUMAN Affects Expression [8]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Increases Expression [30]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [30]
Glutathione synthetase (GSS) OTVSBEIW GSHB_HUMAN Increases Expression [30]
T-complex protein 1 subunit epsilon (CCT5) OTPZ38BT TCPE_HUMAN Affects Expression [8]
Fatty acid synthase (FASN) OTFII9KG FAS_HUMAN Decreases Expression [16]
T-complex protein 1 subunit gamma (CCT3) OTL6EOS1 TCPG_HUMAN Affects Expression [8]
Gastrotropin (FABP6) OTIRQWLW FABP6_HUMAN Increases Expression [31]
Small ribosomal subunit protein mS29 (DAP3) OTNPEZYM RT29_HUMAN Affects Expression [8]
Exportin-2 (CSE1L) OTV2X99A XPO2_HUMAN Affects Expression [8]
Nucleosome assembly protein 1-like 1 (NAP1L1) OTI7WBZV NP1L1_HUMAN Affects Expression [8]
Large ribosomal subunit protein eL27 (RPL27) OTWEOUTX RL27_HUMAN Affects Expression [8]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Activity [32]
Small ribosomal subunit protein uS15 (RPS13) OTOMDIJ2 RS13_HUMAN Affects Expression [8]
Small ribosomal subunit protein eS28 (RPS28) OT12IES1 RS28_HUMAN Affects Expression [8]
Large ribosomal subunit protein eL32 (RPL32) OTKRQJT4 RL32_HUMAN Affects Expression [8]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Affects Expression [8]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Affects Expression [8]
Single-stranded DNA-binding protein, mitochondrial (SSBP1) OTH2PZWH SSBP_HUMAN Affects Expression [8]
Protein kinase C delta type (PRKCD) OTSEH90E KPCD_HUMAN Increases Localization [17]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [27]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [19]
ATP-dependent RNA helicase A (DHX9) OT5AAOQI DHX9_HUMAN Affects Expression [8]
Fibrinogen-like protein 1 (FGL1) OTT0QHQ1 FGL1_HUMAN Affects Expression [8]
Serine/threonine-protein kinase 3 (STK3) OTLNSCQD STK3_HUMAN Affects Expression [8]
DnaJ homolog subfamily C member 3 (DNAJC3) OT7ROIJF DNJC3_HUMAN Decreases Expression [16]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [17]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Localization [30]
Protein Smaug homolog 2 (SAMD4B) OTVRZJ5D SMAG2_HUMAN Affects Expression [8]
Chondroitin sulfate proteoglycan 4 (CSPG4) OTW2D6DE CSPG4_HUMAN Affects Expression [8]
Ribosomal protein eS27-like (RPS27L) OTZWHU0N RS27L_HUMAN Affects Expression [8]
Endoplasmic reticulum metallopeptidase 1 (ERMP1) OT9CIEO2 ERMP1_HUMAN Affects Expression [8]
E3 ubiquitin-protein ligase RBBP6 (RBBP6) OTTVG4HU RBBP6_HUMAN Affects Expression [8]
Out at first protein homolog (OAF) OTOR9CR5 OAF_HUMAN Affects Expression [8]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [18]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [18]
Shieldin complex subunit 2 (SHLD2) OTMLERXL SHLD2_HUMAN Affects Expression [8]
G-protein coupled bile acid receptor 1 (GPBAR1) OT4BKEJ9 GPBAR_HUMAN Decreases Expression [16]
E3 ubiquitin-protein ligase rififylin (RFFL) OT85MGDH RFFL_HUMAN Affects Expression [8]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [33]
AP-2 complex subunit mu (AP2M1) OTQCOSFN AP2M1_HUMAN Affects Expression [8]
Ribosomal protein eL39-like 2 (RPL39L) OTAV1MJQ RL39L_HUMAN Affects Expression [8]
Rho GTPase-activating protein 7 (DLC1) OTP8LMCR RHG07_HUMAN Increases Expression [32]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Expression [16]
Protein sprouty homolog 4 (SPRY4) OT2VK9N0 SPY4_HUMAN Affects Expression [8]
Endosialin (CD248) OTEBWORQ CD248_HUMAN Affects Expression [8]
Soluble lamin-associated protein of 75 kDa (FAM169A) OT2FDMA1 F169A_HUMAN Affects Expression [8]
Sulfotransferase 2A1 (SULT2A1) OT0ISKQ4 ST2A1_HUMAN Increases Sulfation [34]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [11]
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⏷ Show the Full List of 104 DOT(s)

References

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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.
8 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.
9 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.
10 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.
11 Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
12 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.
13 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.
14 Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans. Clin Pharmacol Ther. 2006 May;79(5):449-60.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.
21 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.
22 Hepatic apolipoprotein A-I gene expression in patients with cholesterol gallstones treated with ursodeoxycholic acid. Ann Hepatol. 2002 Apr-Jun;1(2):85-9.
23 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.
24 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.
25 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.
26 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.
27 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.
28 Correlation of chemopreventive efficacy data from the human epidermal cell assay with in vivo data. Anticancer Res. 2000 Jan-Feb;20(1A):27-32.
29 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.
30 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.
31 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.
32 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.
33 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.
34 Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.