Colestolone

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-dodecahydrocyclopenta[a]phenanthren-15-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H44O2
Molar mass400.647 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)CCCC(C)[C@H]1CC(=O)C2=C3CC[C@H]4C[C@H](CC[C@@]4(C3CC[C@]12C)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 (INN, USAN), 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.[1][2][3][4][5] It was first reported in 1977 and was studied until at least 1988, but was never introduced for medical use.[1][3][4]

Colestolone has been found to significantly reduce serum levels of cholesterol both in animals and in humans.[3][4][5] It inhibits multiple relatively early-stage steps in cholesterol biosynthesis such as HMG-CoA reductase[6] and does not appear to affect any late-stage steps (after squalene, specifically).[5] 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.[5]

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.[5]

References

  1. 1 2 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. 1 2 3 "9α-hydroxy-3-oxo-4,24(25)-stigmastadien-26-oic acid derivatives, a process for preparing same and pharmaceutical compositions containing same".
  4. 1 2 3 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. 1 2 3 4 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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