Details of the Drug

General Information of Drug (ID: DM2LZ8F)

Drug Name
Taurocholic Acid
Synonyms
Taurocholic acid; TAUROCHOLIC ACID; Taurocholate; Cholyltaurine; Cholaic acid; N-Choloyltaurine; Cholic acid taurine conjugate; 81-24-3; Taurine, N-choloyl-; Acidum cholatauricum; Taurine Cholate; UNII-5E090O0G3Z; HSDB 832; C26H45NO7S; 3alpha,7alpha,12alpha-Trihydroxy-5beta-cholanic acid 24-taurine; NSC25505; EINECS 201-336-2; NSC 25505; Ethanesulfonic acid, 2-(((3alpha,5beta,7alpha,12alpha)-3,7,12-trihydroxy-24-oxocholan-24-yl)amino)-; 2-((3-alpha,7-alpha,12-alpha-Trihydroxy-24-oxo-5-be ta-cholan-24-yl)amino)ethanesulfonic acid; [3H]taurocholic acid
Indication
Disease Entry ICD 11 Status REF
Type-2 diabetes 5A11 Phase 1/2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 515.7
Logarithm of the Partition Coefficient (xlogp) 2.2
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C26H45NO7S
IUPAC Name
2-[[(4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid
Canonical SMILES
C[C@H](CCC(=O)NCCS(=O)(=O)O)[C@H]1CC[C@@H]2[C@@]1([C@H](C[C@H]3[C@H]2[C@@H](C[C@H]4[C@@]3(CC[C@H](C4)O)C)O)O)C
InChI
InChI=1S/C26H45NO7S/c1-15(4-7-23(31)27-10-11-35(32,33)34)18-5-6-19-24-20(14-22(30)26(18,19)3)25(2)9-8-17(28)12-16(25)13-21(24)29/h15-22,24,28-30H,4-14H2,1-3H3,(H,27,31)(H,32,33,34)/t15-,16+,17-,18-,19+,20+,21-,22+,24+,25+,26-/m1/s1
InChIKey
WBWWGRHZICKQGZ-HZAMXZRMSA-N
Cross-matching ID
PubChem CID
6675
ChEBI ID
CHEBI:28865
CAS Number
81-24-3
DrugBank ID
DB04348
TTD ID
D09NTG
VARIDT ID
DR01121

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bile-salt-activated lipase (CEL) TTTRNQW CEL_HUMAN Inhibitor [2]
Ileal sodium/bile acid cotransporter (SLC10A2) TTPI1M5 NTCP2_HUMAN Modulator [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic solute transporter subunit alpha (SLC51A) DTMEQ32 OSTA_HUMAN Substrate [4]
Apical sodium-dependent bile acid transporter (SLC10A2) DT7JELC NTCP2_HUMAN Substrate [5]
Organic solute transporter subunit beta (SLC51B) DT1V9AJ OSTB_HUMAN Substrate [4]
Organic anion transporting polypeptide 4A1 (SLCO4A1) DT8H2IC SO4A1_HUMAN Substrate [6]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [7]
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DT56EKP NTCP_HUMAN Substrate [8]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [9]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [10]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [11]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [14]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [15]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Gene/Protein Processing [16]
ABC-type organic anion transporter ABCA8 (ABCA8) OTCWLX6N ABCA8_HUMAN Regulation of Drug Effects [17]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Gene/Protein Processing [18]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [19]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Regulation of Drug Effects [20]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Gene/Protein Processing [21]
Biliverdin reductase A (BLVRA) OTTSEKLZ BIEA_HUMAN Gene/Protein Processing [21]
Caveolin-1 (CAV1) OTEZUR1L CAV1_HUMAN Regulation of Drug Effects [22]
Caveolin-2 (CAV2) OT1FGRQX CAV2_HUMAN Regulation of Drug Effects [22]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Post-Translational Modifications [16]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Type-2 diabetes
ICD Disease Classification 5A11
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Ileal sodium/bile acid cotransporter (SLC10A2) DTT SLC10A2 2.54E-01 -0.06 -0.17
Multidrug resistance-associated protein 3 (ABCC3) DTP MRP3 9.87E-01 -1.86E-01 -4.71E-01
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTP OATP2B1 4.61E-01 -7.46E-02 -2.18E-01
Organic solute transporter subunit alpha (SLC51A) DTP OSTalpha 1.79E-01 -1.10E-01 -2.53E-01
Bile salt export pump (ABCB11) DTP BSEP 5.33E-01 -8.86E-02 -2.56E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 1.85E-01 -1.34E-01 -4.20E-01
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTP OATP1A2 1.39E-01 -6.13E-01 -6.63E-01
Multidrug resistance-associated protein 4 (ABCC4) DTP MRP4 6.77E-01 3.03E-02 1.51E-01
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 5.85E-01 1.81E-01 6.68E-01
Organic anion transporting polypeptide 4A1 (SLCO4A1) DTP OATP4A1 5.51E-01 -6.63E-03 -5.81E-02
Apical sodium-dependent bile acid transporter (SLC10A2) DTP ASBT 2.54E-01 -6.48E-02 -1.69E-01
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DTP NTCP 2.93E-01 2.87E-02 1.38E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 2.81E-01 3.67E-02 2.82E-01
Organic solute transporter subunit beta (SLC51B) DTP OSTbeta 4.32E-01 1.33E-01 1.00E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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: 4547).
2 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
3 Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69.
4 Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82.
5 Identification of a region of the ileal-type sodium/bile acid cotransporter interacting with a competitive bile acid transport inhibitor. Biochemistry. 2002 Dec 17;41(50):14916-24.
6 Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
7 Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 2002 Jul 1;64(1):151-8.
8 Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther. 1999 Dec;291(3):1204-9.
9 Characterization of the role of polar amino acid residues within predicted transmembrane helix 17 in determining the substrate specificity of multidrug resistance protein 3. Biochemistry. 2003 Aug 26;42(33):9989-10000.
10 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
12 Identification of multiple binding sites for substrate transport in bovine organic anion transporting polypeptide 1a2. Drug Metab Dispos. 2013 Mar;41(3):602-7.
13 Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta. Mol Pharmacol. 2012 Feb;81(2):273-83.
14 Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63.
15 Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
16 Taurocholate induces cyclooxygenase-2 expression via the sphingosine 1-phosphate receptor 2 in a human cholangiocarcinoma cell line. J Biol Chem. 2015 Dec 25;290(52):30988-1002.
17 Functional analysis of ABCA8, a new drug transporter. Biochem Biophys Res Commun. 2002 Oct 18;298(1):41-5.
18 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.
19 Sorafenib triggers antiproliferative and pro-apoptotic signals in human esophageal adenocarcinoma cells. Dig Dis Sci. 2008 Dec;53(12):3055-64. doi: 10.1007/s10620-008-0294-y. Epub 2008 May 30.
20 Uremic solutes modulate hepatic bile acid handling and induce mitochondrial toxicity. Toxicol In Vitro. 2019 Apr;56:52-61. doi: 10.1016/j.tiv.2019.01.003. Epub 2019 Jan 9.
21 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.
22 Hepatic overexpression of caveolins increases bile salt secretion in mice. Hepatology. 2003 Dec;38(6):1477-88. doi: 10.1016/j.hep.2003.09.011.