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Structure Database (LMSD)

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Common Name

Dehydrolithocholic Acid

Systematic Name

3-Oxo-5β-cholan-24-oic Acid

Synonyms

3-keto LCA
3-keto Lithocholate
3-keto Lithocholic Acid
3-KLCA
3-oxo LCA
3-oxo Lithocholate
3-oxo Lithocholic Acid
DHLCA

LM ID

LMST04010127

Formula

C₂₄H₃₈O₃

Exact Mass

Calculate m/z

374.282096

Sum Composition

ST 24:2;O3

Status

Curated

Show lipids differing only in stereochemistry/bond geometry

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Classification

Biological Context

Dehydrolithocholic acid is a major metabolite of lithocholic acid (LCA).¹ It is formed from LCA by the cytochrome P450 (CYP) isoform CYP3A4. Dehydrolithocholic acid is an agonist of G protein-coupled bile acid activated receptor 1 (GP-BAR1/TGR5; EC50 = 0.27 μM), vitamin D receptor (VDR; EC50 = 3 μM), and farnesoid X receptor (FXR) in cell-based reporter assays.^2,3 It also binds to the human pregnane X receptor (PXR; IC50 = 15 μM) and activates mouse and human PXRs in cell-based reporter assays when used at a concentration of 100 μM.⁴ Dehydrolithocholic acid binds to retinoic acid receptor-related orphan receptor γt (RORγt; Kd = 1.13 μM for the recombinant human ligand-binding domain) and decreases its activity in a cell-based reporter assay when used at a concentration of 10 μM.⁵ It inhibits the differentiation of T helper cells that express IL-17a (TH17 cells) when used at a concentration of 20 μM.

This information has been provided by Cayman Chemical

References

1. Hang, S., Paik, D., Yao, L., et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 576(7785), 143-148 (2019).

2. Sato, H., Macchiarulo, A., Thomas, C., et al. Novel potent and selective bile acid derivatives as TGR5 agonists: Biological screening, structure-activity relationships, and molecular modeling studies. J. Med. Chem. 51(6), 1831-1841 (2008).

3. Deo, A.K., and Bandiera, S.M. 3-Ketocholanoic acid is the major in vitro human hepatic microsomal metabolite of lithocholic acid. Drug Metab. Dispos. 37(9), 1938-1947 (2009).

4. Staudinger, J.L., Goodwin, B., Jones, S.A., et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. USA 98(6), 3369-3374 (2000).

5. Makishima, M., Lu, T.T., Xie, W., et al. Vitamin D receptor as an intestinal bile acid sensor. Science 296(5571), 1313-1316 (2002).

References

Taxonomy Information

Curated from

NCBI taxonomy class

Reference

Homo sapiens (#9606)

Mammalia (#40674)

Simultaneous determination of keto and non-keto bile acids in human serum by gas chromatography with selected ion monitoring.,
J Chromatogr, 1990

Pubmed ID: 2338448

String Representations

InChiKey (Click to copy)

KIQFUORWRVZTHT-OPTMKGCMSA-N

InChi (Click to copy)

InChI=1S/C24H38O3/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/h15-16,18-21H,4-14H2,1-3H3,(H,26,27)/t15-,16-,18+,19-,20+,21+,23+,24-/m1/s1

SMILES (Click to copy)

C1[C@]2(C)[C@@]3([H])CC[C@]4(C)[C@@]([H])([C@]([H])(C)CCC(O)=O)CC[C@@]4([H])[C@]3([H])CC[C@]2([H])CC(=O)C1