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

Molecular Formula	C24H40O3
Molecular Weight	376.5726
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 1410
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 1410

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
[Features of composition of bile acids in duodenal bile in patients with chronic pancreatitis].	2002	12619581
Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate.	2002 Aug	12190957
Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists.	2002 Aug	12119452
Intrahepatic cholestasis of pregnancy: changes in maternal-fetal bile acid balance and improvement by ursodeoxycholic acid.	2002 Jan-Mar	15114292
Postprandial changes in serum unconjugated bile acid concentrations in healthy beagles.	2002 Jun	12061521
Identification of membrane-type receptor for bile acids (M-BAR).	2002 Nov 15	12419312
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
Bile acids enhance low density lipoprotein receptor gene expression via a MAPK cascade-mediated stabilization of mRNA.	2002 Oct 4	12149270
Functional interaction of lithocholic acid conjugates with M3 muscarinic receptors on a human colon cancer cell line.	2002 Oct 9	12379313
Calcium affects biomarkers of colon carcinogenesis after right hemicolectomy.	2002 Sep	12486870
Intestinal bile acids can bind to and activate the vitamin D receptor.	2002 Sep	12296454
Kinetic characterization of native and cysteine 112-modified glutathione S-transferase A1-1: reassessment of nonsubstrate ligand binding.	2002 Sep 10	12206662
Synthesis of [3,4-(13)c(2)]-enriched bile salts as NMR probes of protein-ligand interactions.	2002 Sep 20	12227809
Does ursodeoxycholic acid change the proliferation of the colorectal mucosa?. A randomized, placebo-controlled study.	2003	14707397
Urinary excretion of bile acids in bile duct-ligated rats.	2003	12825132
Influence of breast feeding, and adapted and hydrolyzed formulas on biliary bile acids in newborn guinea pigs.	2003	12566682
Activation of muscarinic receptor signaling by bile acids: physiological and medical implications.	2003 Aug	12924634
Sex steroid receptors, secondary bile acids and colorectal cancer. A possible mechanism of interaction.	2003 Dec	15206167
Synthesis of ester-linked lithocholic acid dimers.	2003 Dec	14643877
Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone.	2003 Feb 1	12604236
[Functional analysis of drug metabolizing enzymes using gene knockout animals].	2003 Jul	12875239
Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases.	2003 Mar 10	12618885
A G protein-coupled receptor responsive to bile acids.	2003 Mar 14	12524422
Effects on cell proliferation, activator protein-1 and genotoxicity by fecal water from patients with colorectal adenomas.	2003 May	12795469
Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity.	2003 May 16	12637555
Induction of ABCC3 (MRP3) by pregnane X receptor activators.	2003 Nov	14570758
Effect of tartaric acid and dietary fibre from sun-dried raisins on colonic function and on bile acid and volatile fatty acid excretion in healthy adults.	2003 Oct	13129449
Comparison among fecal secondary bile acid levels, fecal microbiota and Clostridium scindens cell numbers in Japanese.	2004	15215624
Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids.	2004 Dec	15375181
Effects of bile acids on proliferation and production of proteinase activity of Uronema marinum (Ciliophora: Scuticociliatida).	2004 Dec 13	15672881
Bile acid amidoalcohols: simple organogelators.	2004 Dec 15	15556372
Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography-mass spectrometry-single ion monitoring in faeces.	2004 Dec 25	15556534
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
The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion.	2004 Mar 5	14684751
Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting human insulins.	2004 May 25	15147182
The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity.	2004 Nov 19	15358766
Modified oligonucleotides containing lithocholic acid in their backbones: their enhanced cellular uptake and their mimicking of hairpin structures.	2004 Nov 5	15515100
Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity.	2004 Oct	15554243
Properties of a thermostable extracellular lipase from Bacillus megaterium AKG-1.	2005	15812860
Generation of a single-chain Fv fragment for the monitoring of deoxycholic acid residues anchored on endogenous proteins.	2005 Apr	15784283
Chemical synthesis of 24-beta-D-galactopyranosides of bile acids: a new type of bile acid conjugates in human urine.	2005 Apr	15784232
Molecular and functional comparison of 1,25-dihydroxyvitamin D(3) and the novel vitamin D receptor ligand, lithocholic acid, in activating transcription of cytochrome P450 3A4.	2005 Apr 1	15578590
Novel pathways of bile acid metabolism involving CYP3A4.	2005 Feb 21	15708356
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.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 02:17:43 UTC 2023` Edited by `admin` on `Thu Jul 06 02:17:43 UTC 2023`
Record UNII	5QU0I8393U
Record Status	`Validated (UNII)`
Record Version

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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