Structural Formula

Lithocholic acid

Formula

C24-H40-O3

Lithocholic acid

Description

Lithocholic acid is manufactured by NZP.

The "secondary" bile acid, lithocholic acid, is produced in humans in small quantities from the salts of glycochenodeoxycholic and taurochenodeoxycholic acid1 by bacteria resident in the colon. Once formed, some of the lithocholic acid is absorbed by the intestine and returned to the liver where it is conjugated and/or sulfated and released into the gall bladder as a minor component of bile.

It has been implicated in human and experimental animal carcinogenesis.2  Conversely, preliminary in vitro research suggests that LCA selectively kills neuroblastoma cells, while sparing normal neuronal cells and is cytotoxic to numerous other malignant cell types at physiologically relevant concentrations3.

Recently lithocholic acid derivatives have been identified as potent agonists for the TGR5 receptor4 and the VDR receptor5.

There is now a considerable body of knowledge describing the agonist activity of bile acids on the FXR receptor.  LCA, especially as the tauro-conjugate, has been shown to be one of the agonists6 and while there might be evidence of its toxicity in some animal models, the functional toxicity in humans is in question, as a consequence of efficient human detoxification biology7.  This indicates that with the ready availability of Dextra-NZP’s lithocholic acid, growth in research about the possibilities of using LCA derivatives in drug development becomes a strong possibility.

Use of Chemical

Lithocholic acid is used in small quantities in photoresists. More recently, it has attracted attention in drug development.

Specifications

  • CAS Number: 434-13-9
  • Molecular Weight: 376.6
  • Solubility: Sparingly soluble in water. Soluble in hot ethanol and other polar organic solvents and glacial acetic acid. Insoluble in petroleum ether.
  • Packaging: Lithocholic is sealed in a polyethylene liner and packed in foil bags or for larger quantities; in plastic buckets. Customer specific packaging can be provided.

Relevant Publications

1 Also manufactured at Dextra & NZP.
2 Kozoni, V.; Tsioulias, G; Shiff, S; Rigas, B (2000). "The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: Differential effect on apoptosis in the presence of a colon carcinogen". Carcinogenesis 21 (5): 999–1005. doi:10.1093/carcin/21.5.999. PMID 10783324.
3 Goldberg, AA; Beach, A; Davies, GF; Harkness, TA; Leblanc, A; Titorenko, VI (2011). "Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells". Oncotarget 2 (10): 761–82. PMC 3248158. PMID 21992775.
4 Novartis Patent Appl. US 2009/0258847 and 2009/0215044.
5 Nihon University Patent Appl. US 2010/0204191.
6 Rizzo G, Renga B, Mencarelli A, Pellicciari R, Fiorucci S. “Role of FXR in regulating bile acid homeostasis and relevance for human diseases”.  Curr Drug Targets Immune Endocr Metabol Disord. 2005 Sep;5(3):289-303.
7 Hofmann AF., (2004). “Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity”.
Drug Metab Rev. Oct;36(3-4):703-22.
8 US Patent: 6258508 (2001).