LITHOCHOLIC ACID

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H40O3
Molecular Weight	376.5726
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O

InChI

InChIKey=SMEROWZSTRWXGI-HVATVPOCSA-N

InChI=1S/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/t15-,16-,17-,18+,19-,20+,21+,23+,24-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8862472 | https://www.ncbi.nlm.nih.gov/pubmed/11248085 | https://www.ncbi.nlm.nih.gov/pubmed/21992775

Lithocholic acid (LCA) is a secondary bile acid that is formed in the intestine by the bacteria and can activate the pregnane X and the vitamin D receptors. In humans, elevated levels of LCA are found in patients suffering from the chronic cholestatic liver disease. Whereas in normal colonic epithelium lithocholic acid promotes apoptosis, it has been shown to possess anti-tumor effect in human neuroblastoma cell lines. In addition, was proposed, that LCA could kill cancer cells and increase the longevity of non-cancerous cells by causing quite opposite effects on the same kind of mitochondria-confined processes in these two different cell types.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nuclear receptor subfamily 1 group I member 2 8 Target ID: O75469\|\|\|Q9UJ26 Gene ID: 8856.0 Gene Symbol: NR1I2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11248085	Activator 1430
Vitamin D3 receptor 9 Target ID: P11473 Gene ID: 7421.0 Gene Symbol: VDR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28318299	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cholestatic liver disease 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8862472	Diagnostic		Natural Metabolite	Unknown Approved Use Unknown
Neuroblastoma 25 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21992775	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Cholesterol 7alpha-hydroxylase. 2. Biochemical properties and participation of endogenous cholesterol in the assay in vitro.	1975 Jun 16	1175606
Endogenous bile acids are ligands for the nuclear receptor FXR/BAR.	1999 May	10360171
Bile acids: natural ligands for an orphan nuclear receptor.	1999 May 21	10334993
Identification of a nuclear receptor for bile acids.	1999 May 21	10334992
LUV's lipid composition modulates diffusion of bile acids.	2001 Apr	11369325
Alterations in intestinal microflora, faecal bile acids and short chain fatty acids in dextran sulphate sodium-induced experimental acute colitis in rats.	2001 Feb	11246608
Determination of bile acids in biological fluids by liquid chromatography-electrospray tandem mass spectrometry.	2001 Jan	11160372
Enantioselective inhibition of the binding of rac-profens to human serum albumin induced by lithocholate.	2001 Jul	11400191
The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity.	2001 Mar 13	11248085
Chemical genomics: functional analysis of orphan nuclear receptors in the regulation of bile acid metabolism.	2001 Nov	11607932
Photoaffinity labeling of human retinoid X receptor beta (RXRbeta) with 9-cis-retinoic acid: identification of phytanic acid, docosahexaenoic acid, and lithocholic acid as ligands for RXRbeta.	2002 Apr 16	11939783
Advantages of in vitro cytotoxicity testing by using primary rat hepatocytes in comparison with established cell lines.	2002 Aug	12238146
Biotinylated lithocholic acids for affinity chromatography of mammalian DNA polymerases alpha and beta.	2002 Feb 11	11814779
Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism.	2002 Feb 7	11814708
Nuclear xeno-sensors as receptors for cholestatic bile acids: the second line of defense.	2002 Jan	11786981
Postprandial changes in serum unconjugated bile acid concentrations in healthy beagles.	2002 Jun	12061521
Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor.	2002 Mar	11893771
Unconjugated bile acids modulate adult and neonatal neutrophil chemotaxis induced in vitro by N-formyl-met-leu-phe-peptide.	2002 Mar	11861947
Vitamin D receptor as an intestinal bile acid sensor.	2002 May 17	12016314
The effect of charge reversal mutations in the alpha-helical region of liver fatty acid binding protein on the binding of fatty-acyl CoAs, lysophospholipids and bile acids.	2002 Oct	12479568
Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist.	2002 Oct	12235229
Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways.	2002 Oct 3	12360401
Bile acids enhance low density lipoprotein receptor gene expression via a MAPK cascade-mediated stabilization of mRNA.	2002 Oct 4	12149270
Calcium affects biomarkers of colon carcinogenesis after right hemicolectomy.	2002 Sep	12486870
A monoclonal antibody-based enzyme-linked immunosorbent assay of glycolithocholic acid sulfate in human urine for liver function test.	2002 Sep	12231118
Does ursodeoxycholic acid change the proliferation of the colorectal mucosa?. A randomized, placebo-controlled study.	2003	14707397
Influence of breast feeding, and adapted and hydrolyzed formulas on biliary bile acids in newborn guinea pigs.	2003	12566682
Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone.	2003 Feb 1	12604236
Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7.	2003 Feb 1	12527334
[Functional analysis of drug metabolizing enzymes using gene knockout animals].	2003 Jul	12875239
New insights into the mechanisms of vitamin D action.	2003 Mar 1	12577303
Effects on cell proliferation, activator protein-1 and genotoxicity by fecal water from patients with colorectal adenomas.	2003 May	12795469
Comparison among fecal secondary bile acid levels, fecal microbiota and Clostridium scindens cell numbers in Japanese.	2004	15215624
Structural relationship of lithocholic acid derivatives binding to the N-terminal 8-kDa domain of DNA polymerase beta.	2004 Aug 24	15311928
DNA hypomethylation induced by non-genotoxic carcinogens in mouse and rat colon.	2004 Aug 30	15279894
Structural determinants for vitamin D receptor response to endocrine and xenobiotic signals.	2004 Jan	14525957
Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation.	2004 Jan	13130122
Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice.	2004 Mar 19	14681232
Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting human insulins.	2004 May 25	15147182
Properties of a thermostable extracellular lipase from Bacillus megaterium AKG-1.	2005	15812860
Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice.	2005 Jan	15619241
Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative.	2005 Jan	15489543
Affinity capture of a mammalian DNA polymerase beta by inhibitors immobilized to resins used in solid-phase organic synthesis.	2005 Jan-Feb	15656580
Lithocholic acid decreases expression of UGT2B7 in Caco-2 cells: a potential role for a negative farnesoid X receptor response element.	2005 Jul	15821044
Vitamin D receptor-dependent regulation of colon multidrug resistance-associated protein 3 gene expression by bile acids.	2005 Jun 17	15824121

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

It was discovered, that at concentrations that were not cytotoxic to primary cultures of human neurons, lithocholic acid (LCA) killed the neuroblastoma (NB) cell lines BE(2)-m17, SK-n-SH, SK-n-MCIXC and Lan-1. In BE(2)-m17, SK-n-SH and SK-n-MCIXC cells, the LCA anti-tumor effect was due to apoptotic cell death. In contrast, the LCA-triggered death of Lan-1 cells was not caused by apoptosis. It was found that LCA (0-250 uM) significantly increases the activity of caspase-8 in BE(2)-m17 and SK-n-MCIXC. The extent to which caspase-8 was activated by LCA in these two cell lines was correlated with the degree of their sensitivity to the cytotoxic, apoptosis-inducing and hydrogen peroxide-sensitizing effects of LCA. It was proposed that the LCA-dependent activation of caspase-8 seen in BE(2)-m17 and SK-n-MCIXC cells could be responsible not only for the direct proteolytic activation of caspase-3 but also for MOMP (perhaps, due to BID cleavage by caspase-8) and the resulting initiation of the intrinsic apoptotic death pathway observed in these NB cells.

Name

Type

Language

LITHOCHOLIC ACID

Common Name

English

LITHOCHOLIC ACID [MI]

Common Name

English

3.ALPHA.-HYDROXYCHOLANIC ACID

Systematic Name

English

17.BETA.-(1-METHYL-3-CARBOXYPROPYL)ETIOCHOLAN-3.ALPHA.-OL

Common Name

English

URSODEOXYCHOLIC ACID IMPURITY C [EP IMPURITY]

Common Name

English

LITHOCHOLIC ACID [EP IMPURITY]

Common Name

English

NSC-683770

Code

English

LITHOCHOLIC ACID [HSDB]

Common Name

English

NSC-657956

Code

English

Code System Code Type Description

CAS

434-13-9