Details of the Drug Combination

General Information of Drug Combination (ID: DCBU4FI)

Drug Combination Name
Colesevelam Chenodiol
Indication
Disease Entry Status REF
Severe Obesity Phase 4 [1]
Component Drugs Colesevelam   DMMUFKM Chenodiol   DMQ8JIK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Colesevelam
Disease Entry ICD 11 Status REF
Hypercholesterolaemia 5C80.0 Approved [2]
Indication(s) of Chenodiol
Disease Entry ICD 11 Status REF
Cholelithiasis DC11 Approved [2]
Chenodiol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Farnesoid X-activated receptor (FXR) TTS4UGC NR1H4_HUMAN Modulator [11]
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Chenodiol Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [5]
Cytochrome P450 8B1 (CYP8B1) DETL4WB CP8B1_HUMAN Metabolism [13]
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Chenodiol Interacts with 74 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [3]
7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase (CYP8B1) OTRI4UR1 CP8B1_HUMAN Decreases Expression [14]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Activity [15]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1) OTO7FJA9 DHI1_HUMAN Decreases Activity [16]
Gastrotropin (FABP6) OTIRQWLW FABP6_HUMAN Increases Expression [4]
Fibroblast growth factor 19 (FGF19) OT2DVJWY FGF19_HUMAN Increases Expression [17]
Serum paraoxonase/arylesterase 1 (PON1) OTD0Z2XO PON1_HUMAN Decreases Expression [17]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [17]
Sulfotransferase 2A1 (SULT2A1) OT0ISKQ4 ST2A1_HUMAN Decreases Expression [18]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [19]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Increases Expression [20]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Expression [21]
Sulfotransferase 1C2 (SULT1C2) OT07MMZS ST1C2_HUMAN Increases Expression [3]
Solute carrier family 22 member 1 (SLC22A1) OT7817I4 S22A1_HUMAN Decreases Expression [3]
Fatty acid-binding protein, brain (FABP7) OTRE2H4G FABP7_HUMAN Decreases Expression [3]
Sulfotransferase 1B1 (SULT1B1) OTH0RQYA ST1B1_HUMAN Decreases Expression [3]
Aflatoxin B1 aldehyde reductase member 3 (AKR7A3) OTW3GO4Y ARK73_HUMAN Decreases Expression [3]
Apolipoprotein M (APOM) OTI3FQQC APOM_HUMAN Decreases Expression [3]
Beta-2-glycoprotein 1 (APOH) OTFMUX6O APOH_HUMAN Decreases Expression [3]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [3]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Expression [3]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Decreases Expression [3]
Apolipoprotein A-IV (APOA4) OT466POQ APOA4_HUMAN Decreases Expression [3]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [3]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Expression [3]
Aldo-keto reductase family 1 member C4 (AKR1C4) OTW2MMOF AK1C4_HUMAN Decreases Expression [3]
Acetyl-CoA acetyltransferase, mitochondrial (ACAT1) OTJC60Q7 THIL_HUMAN Decreases Expression [3]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [3]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Increases Expression [3]
Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACADSB) OTDO6HBG ACDSB_HUMAN Decreases Expression [3]
Sulfotransferase 1E1 (SULT1E1) OTGPJ517 ST1E1_HUMAN Decreases Expression [3]
Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2) OTC3RUN9 HMCS2_HUMAN Decreases Expression [3]
Apolipoprotein C-IV (APOC4) OTE8ZUXY APOC4_HUMAN Decreases Expression [3]
Peroxisomal biogenesis factor 3 (PEX3) OTGZ7ME2 PEX3_HUMAN Decreases Expression [3]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Decreases Expression [3]
Bile acid-CoA:amino acid N-acyltransferase (BAAT) OTTMB3JY BAAT_HUMAN Decreases Expression [3]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Decreases Expression [3]
Acyl-CoA dehydrogenase family member 11 (ACAD11) OT3T9HAX ACD11_HUMAN Decreases Expression [3]
ATP-binding cassette sub-family G member 8 (ABCG8) OTIJ76XW ABCG8_HUMAN Increases Expression [3]
Angiopoietin-related protein 3 (ANGPTL3) OTCD5Z9W ANGL3_HUMAN Decreases Expression [3]
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Decreases Expression [3]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Decreases Expression [3]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [22]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Increases Expression [23]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Decreases Expression [24]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases Expression [9]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [25]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Increases Expression [26]
E-selectin (SELE) OT33RZWY LYAM2_HUMAN Increases Expression [9]
Nuclear receptor subfamily 1 group D member 1 (NR1D1) OTJ38PTB NR1D1_HUMAN Affects Expression [27]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Increases Expression [28]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [29]
Coronin-1A (CORO1A) OTVAZOHC COR1A_HUMAN Decreases Expression [30]
Nuclear receptor ROR-alpha (RORA) OTGQT12P RORA_HUMAN Affects Expression [27]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [31]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Affects Localization [32]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Increases Expression [7]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [7]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [25]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Affects Expression [27]
Hematopoietically-expressed homeobox protein HHEX (HHEX) OTLIUVYX HHEX_HUMAN Increases Expression [29]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Expression [14]
Nuclear receptor subfamily 1 group D member 2 (NR1D2) OT9CVF41 NR1D2_HUMAN Affects Expression [27]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Increases Expression [10]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [33]
Organic solute transporter subunit beta (SLC51B) OT4WYPSR OSTB_HUMAN Increases Expression [33]
G-protein coupled bile acid receptor 1 (GPBAR1) OT4BKEJ9 GPBAR_HUMAN Increases Expression [14]
Scavenger receptor class B member 1 (SCARB1) OTAE1UA1 SCRB1_HUMAN Increases Expression [34]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [14]
Homeobox protein CDX-2 (CDX2) OTCG4TSY CDX2_HUMAN Increases Expression [32]
ATP-binding cassette sub-family G member 5 (ABCG5) OT1OMY93 ABCG5_HUMAN Increases Expression [14]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Expression [14]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Decreases Response To Substance [7]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Decreases Response To Substance [35]
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⏷ Show the Full List of 74 DOT(s)

References

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2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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5 Human UDP-glucuronosyltransferase (UGT)1A3 enzyme conjugates chenodeoxycholic acid in the liver. Hepatology. 2006 Nov;44(5):1158-70.
6 Regulation of the human bile acid UDP-glucuronosyltransferase 1A3 by the farnesoid X receptor and bile acids. J Hepatol. 2010 Apr;52(4):570-8.
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11 Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7.
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13 Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1. Biol Chem. 2019 Apr 24;400(5):625-628.
14 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.
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17 A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids. J Lipid Res. 2006 Feb;47(2):384-92.
18 Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase. Drug Metab Pharmacokinet. 2006 Aug;21(4):315-23.
19 Peroxisome proliferator-activated receptor alpha activates cyclooxygenase-2 gene transcription through bile acid transport in human colorectal cancer cell lines. J Gastroenterol. 2008;43(7):538-49.
20 The role of lithocholic acid in the regulation of bile acid detoxication, synthesis, and transport proteins in rat and human intestine and liver slices. Toxicol In Vitro. 2011 Feb;25(1):80-90.
21 Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis. PLoS One. 2012;7(1):e30443.
22 Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.
23 Retinoid X receptor (RXR) agonist-induced antagonism of farnesoid X receptor (FXR) activity due to absence of coactivator recruitment and decreased DNA binding. J Biol Chem. 2003 Mar 21;278(12):10028-32. doi: 10.1074/jbc.M208312200. Epub 2003 Jan 7.
24 Differentiated CaCo-2 cells as an in-vitro model to evaluate de-novo apolipoprotein A-I production in the small intestine. Eur J Gastroenterol Hepatol. 2009 Jun;21(6):642-9. doi: 10.1097/meg.0b013e328321b0c8.
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26 Fibrates suppress chenodeoxycholic acid-induced RANTES expression through inhibition of NF-kappaB activation. Eur J Pharmacol. 2002 Jul 12;448(1):19-26. doi: 10.1016/s0014-2999(02)01902-7.
27 System analysis of cross-talk between nuclear receptors reveals an opposite regulation of the cell cycle by LXR and FXR in human HepaRG liver cells. PLoS One. 2019 Aug 22;14(8):e0220894. doi: 10.1371/journal.pone.0220894. eCollection 2019.
28 Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J Biol Chem. 2003 Dec 19;278(51):51085-90. doi: 10.1074/jbc.M308321200. Epub 2003 Oct 2.
29 Hematopoietically expressed homeobox is a target gene of farnesoid X receptor in chenodeoxycholic acid-induced liver hypertrophy. Hepatology. 2009 Mar;49(3):979-88. doi: 10.1002/hep.22712.
30 Downregulation of TACO gene transcription restricts mycobacterial entry/survival within human macrophages. FEMS Microbiol Lett. 2005 Sep 1;250(1):137-44. doi: 10.1016/j.femsle.2005.06.056.
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32 Inflammatory mediators of esophagitis alter p27 Kip1 expression in esophageal epithelial cells. J Pediatr Gastroenterol Nutr. 2010 Nov;51(5):556-62. doi: 10.1097/MPG.0b013e3181ecd65d.
33 Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1124-30. doi: 10.1152/ajpgi.00539.2005. Epub 2006 Jan 19.
34 Farnesoid X receptor induces murine scavenger receptor Class B type I via intron binding. PLoS One. 2012;7(4):e35895. doi: 10.1371/journal.pone.0035895. Epub 2012 Apr 23.
35 Lack of response to chenodeoxycholic acid in obese and non-obese patients. Role of cholesterol synthesis and possible response to ursodeoxycholic acid. Gut. 1980 Dec;21(12):1082-6. doi: 10.1136/gut.21.12.1082.