Cholic Acid

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Also known as Cholalic acidCholbamE1000KolbamNSC-6135OrphacolSID26754161SID26754162SID50085904Cholic_acid

Summary

Cholic Acid (CHEMBL205596) is an approved small molecule (ATC A05AA03) targeting GPBAR1 and NR1H4; indicated across 6 conditions including liver disorder and inborn errors of metabolism.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: A05AA03
  • Targets: 2 (GPBAR1, NR1H4)
  • Indications: 6 conditions
  • Clinical trials: 6
  • Chemistry: 408.6 Da · C24H40O5

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL205596
NameCholic Acid
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID221493
ChEBICHEBI:16359
ATCA05AA03
Molecular formulaC24H40O5
Molecular weight408.6
InChIKeyBHQCQFFYRZLCQQ-OELDTZBJSA-N

SMILES: C[C@H](CCC(=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

IUPAC name: (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]pentanoic acid

ChEBI definition: A bile acid that is 5β-cholan-24-oic acid bearing three α-hydroxy substituents at position 3, 7 and 12.

Other ChEBI roles (chemical / environmental): human metabolite, mouse metabolite.

Also known as: Cholalic acid, Cholic acid, Cholbam, E1000, Kolbam, NSC-6135, Orphacol, cholic acid, SID26754161, SID26754162, SID50085904, Cholic Acid

Parent form; salt/anhydrous children: CHEMBL1334097, CHEMBL1421383, CHEMBL3187726

Patent coverage: 29,911 distinct patent families (76,195 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
GPBAR1GPBA receptorFull agonist50.6%Q8TDU6
NR1H4Farnesoid X receptorAgonist50.7%Q96RI1

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: G-protein coupled bile acid receptor 1, Bile acid receptor, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, Cytochrome P450 3A4, Cruzipain, G-protein coupled bile acid receptor 1.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 17 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
Q80SS65.28IC505300nMCHEMBL_ACT_3500482
GPBAR15.22IC506000nMCHEMBL_ACT_3500451
GPBAR15.11EC507720nMCHEMBL_ACT_25994695
GPBAR15.11EC507720nMCHEMBL_ACT_29078712

Target pathways

Aggregated over 2 target gene(s): GPBAR1, NR1H4.

Top Reactome pathways

10 total, by targets touching each:

PathwayTargetsGenes
Recycling of bile acids and salts1NR1H4
Synthesis of bile acids and bile salts1NR1H4
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol1NR1H4
Synthesis of bile acids and bile salts via 27-hydroxycholesterol1NR1H4
PPARA activates gene expression1NR1H4
Endogenous sterols1NR1H4
Class A/1 (Rhodopsin-like receptors)1GPBAR1
Nuclear Receptor transcription pathway1NR1H4
SUMOylation of intracellular receptors1NR1H4
G alpha (s) signalling events1GPBAR1

Dominant GO biological processes

GO termTargets
cellular response to bile acid2
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway1
positive regulation of ERK1 and ERK2 cascade1
energy homeostasis1
positive regulation of cholangiocyte proliferation1
regulation of bicellular tight junction assembly1
signal transduction1
G protein-coupled receptor signaling pathway1
negative regulation of transcription by RNA polymerase II1
intracellular glucose homeostasis1
regulation of DNA-templated transcription1
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
inflammatory response1
cell-cell junction assembly1

Indications & clinical

Indications

6 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
liver disorder4MONDO:0005154EFO:0001421
inborn errors of metabolism4MONDO:0019052MONDO:0019052
fatty liver disease2MONDO:0004790HP:0001397
Smith-Lemli-Opitz syndrome1MONDO:0010035MONDO:0010035

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 6.

Phase distribution

PhaseTrials
PHASE32
Not specified2
PHASE21
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01115582PHASE3COMPLETEDEfficacy of To Be Marketed (TBM) Cholic Acid Capsules Used to Treat Children With Inborn Errors of Bile Acid Synthesis
NCT01438411PHASE3COMPLETEDOpen Label, Continuation Study of Cholic Acid in Subjects With Inborn Errors of Bile Acid Synthesis
NCT00457639PHASE2COMPLETEDCholic Acid for Hepatic Steatosis in Lipodystrophy
NCT03720990PHASE1/PHASE2COMPLETEDSmith-Lemli-Opitz Syndrome and Cholic Acid
NCT03115086Not specifiedACTIVE_NOT_RECRUITINGThe REPLACE Registry for Cholbam® (Cholic Acid)
NCT00004442Not specifiedTERMINATEDStudy of Bile Acids in Patients With Peroxisomal Disorders

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

55 molecules share ≥1 primary target. Top 55 by shared-target count:

MoleculeSourceStatusShared targets
CHENODIOLChEMBL + PubChemPhase 4 (approved)GPBAR1, NR1H4
DEOXYCHOLIC ACIDChEMBLPhase 4 (approved)GPBAR1, NR1H4
OBETICHOLIC ACIDChEMBLPhase 4 (approved)GPBAR1, NR1H4
TAURURSODIOLChEMBLPhase 4 (approved)GPBAR1, NR1H4
TERN-101ChEMBLPhase 2GPBAR1, NR1H4
FULVESTRANTChEMBL + PubChemPhase 4 (approved)NR1H4
REGORAFENIBChEMBL + PubChemPhase 4 (approved)NR1H4
ACETAMINOPHENChEMBLPhase 4 (approved)NR1H4
ATORVASTATINChEMBLPhase 4 (approved)NR1H4
BENZBROMARONEChEMBLPhase 4 (approved)NR1H4
CLOFAZIMINEChEMBLPhase 4 (approved)NR1H4
CLOTRIMAZOLEChEMBLPhase 4 (approved)NR1H4
CYCLOSPORINEChEMBLPhase 4 (approved)NR1H4
DICLOFENACChEMBLPhase 4 (approved)NR1H4
EPALRESTATChEMBLPhase 4 (approved)NR1H4
ESTRADIOLChEMBLPhase 4 (approved)GPBAR1
FELODIPINEChEMBLPhase 4 (approved)NR1H4
FLUTRIMAZOLEChEMBLPhase 4 (approved)NR1H4
IVERMECTINChEMBLPhase 4 (approved)NR1H4
KETOCONAZOLEChEMBLPhase 4 (approved)NR1H4
LEVOTHYROXINEChEMBLPhase 4 (approved)NR1H4
LORATADINEChEMBLPhase 4 (approved)NR1H4
NIMODIPINEChEMBLPhase 4 (approved)NR1H4
ODEVIXIBATChEMBLPhase 4 (approved)NR1H4
PRANLUKASTChEMBLPhase 4 (approved)NR1H4
PRASTERONEChEMBLPhase 4 (approved)GPBAR1
PREDNISOLONEChEMBLPhase 4 (approved)GPBAR1
PROGESTERONEChEMBLPhase 4 (approved)GPBAR1
RALOXIFENEChEMBLPhase 4 (approved)NR1H4
REPAGLINIDEChEMBLPhase 4 (approved)NR1H4
RIMONABANTChEMBLPhase 4 (approved)NR1H4
SIMVASTATINChEMBLPhase 4 (approved)NR1H4
SULCONAZOLEChEMBLPhase 4 (approved)NR1H4
SUNITINIBChEMBLPhase 4 (approved)NR1H4
TESTOSTERONEChEMBLPhase 4 (approved)GPBAR1
TROGLITAZONEChEMBLPhase 4 (approved)NR1H4
URSODIOLChEMBLPhase 4 (approved)GPBAR1
ZAFIRLUKASTChEMBLPhase 4 (approved)NR1H4
ANDROGRAPHOLIDEChEMBLPhase 3NR1H4
CILOFEXORChEMBLPhase 3NR1H4
ELOBIXIBATChEMBLPhase 3NR1H4
GLYCOCHOLIC ACIDChEMBLPhase 3GPBAR1
NORUCHOLIC ACIDChEMBLPhase 3GPBAR1
TAUROLITHOCHOLIC ACIDChEMBLPhase 3GPBAR1
VIDOFLUDIMUSChEMBLPhase 3NR1H4
NIDUFEXORChEMBLPhase 2NR1H4
PX-102ChEMBLPhase 2NR1H4
STANOLONEChEMBLPhase 2GPBAR1
TAURODEOXYCHOLIC ACIDChEMBLPhase 2GPBAR1
TROPIFEXORChEMBLPhase 2NR1H4
TUROFEXORATE ISOPROPYLChEMBLPhase 2NR1H4
URSOLIC ACIDChEMBLPhase 2GPBAR1
BosentanPubChemApprovedNR1H4
OlanzapinePubChemApprovedNR1H4
rifampinPubChemApprovedNR1H4