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Colestolone

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Chemical compound Pharmaceutical compound
Colestolone
Clinical data
Other names5α-Cholest-8(14)-en-3β-ol-15-one; 3β-Hydroxy-5α-cholest-8(14)-en-15-one
Identifiers
IUPAC name
  • (3S,5S,10S,13R,17R)-3-Hydroxy-10,13-dimethyl-17-(6-methylheptan-2-yl)-1,2,3,4,5,6,7,9,11,12,16,17-dodecahydrocyclopentaphenanthren-15-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H44O2
Molar mass400.647 g·mol
3D model (JSmol)
SMILES
  • CC(C)CCCC(C)1CC(=O)C2=C3CC4C(CC4(C3CC12C)C)O
InChI
  • InChI=1S/C27H44O2/c1-17(2)7-6-8-18(3)23-16-24(29)25-21-10-9-19-15-20(28)11-13-26(19,4)22(21)12-14-27(23,25)5/h17-20,22-23,28H,6-16H2,1-5H3/t18?,19-,20-,22?,23+,26-,27+/m0/s1
  • Key:LINVVMHRTUSXHL-NDNSGUFDSA-N

Colestolone (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name), also known as 5α-cholest-8(14)-en-3β-ol-15-one, is a potent inhibitor of sterol biosynthesis which is described as a hypocholesterolemic (lipid-lowering) agent. It was first reported in 1977 and was studied until at least 1988, but was never introduced for medical use.

Colestolone has been found to significantly reduce serum levels of cholesterol both in animals and in humans. It inhibits multiple relatively early-stage steps in cholesterol biosynthesis such as HMG-CoA reductase and does not appear to affect any late-stage steps (after squalene, specifically). Unlike late-stage cholesterol biosynthesis inhibitors like triparanol and azacosterol, no accumulation of sterols has been observed in animals treated with colestolone, suggesting that it does not share the toxicity of late-stage cholesterol biosynthesis inhibitors.

In addition to its potent inhibition of cholesterol biosynthesis, it is notable that colestolone also happens to serve as a precursor of cholesterol, and is efficiently converted into it in rat liver homogenates and upon oral administration to rats.

References

  1. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 646–. ISBN 978-1-4757-2085-3.
  2. Daniel Lednicer (4 March 2009). Strategies for Organic Drug Synthesis and Design. John Wiley & Sons. pp. 186–. ISBN 978-0-470-39959-0.
  3. ^ "9α-hydroxy-3-oxo-4,24(25)-stigmastadien-26-oic acid derivatives, a process for preparing same and pharmaceutical compositions containing same".
  4. ^ Schroepfer GJ, Chu AJ, Needleman DH, Izumi A, Nguyen PT, Wang KS, Little JM, Sherrill BC, Kisic A (1988). "Inhibitors of sterol synthesis. Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one after intravenous administration to bile duct-cannulated rats". J. Biol. Chem. 263 (9): 4110–23. doi:10.1016/S0021-9258(18)68897-0. PMID 3346239.
  5. ^ Schroepfer GJ, Parish EJ, Kisic A, Jackson EM, Farley CM, Mott GE (1982). "5 alpha-Cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of sterol biosynthesis, lowers serum cholesterol and alters distributions of cholesterol in lipoproteins in baboons". Proc. Natl. Acad. Sci. U.S.A. 79 (9): 3042–6. Bibcode:1982PNAS...79.3042S. doi:10.1073/pnas.79.9.3042. PMC 346345. PMID 6953447.
  6. Pharmaceutical R&D costs, risks, and rewards. DIANE Publishing. 1993. pp. 25–. ISBN 978-1-4289-2103-0.
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