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Δ4-Tibolone

Δ4-Tibolone
Δ4-Tibolone.svg
Δ4-Tibolone molecule ball.png
Clinical data
Other namesORG-OM-38; Delta-4-Tibolone; 7α-Methylnorethisterone; 7α-Methyl-17α-ethynyl-19-nortestosterone; 17α-Ethynyl-17β-hydroxy-7α-methyl-4-estren-3-one
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC21H28O2
Molar mass312.453 g/mol g·mol−1
3D model (JSmol)

Δ4-Tibolone (developmental code name ORG-OM-38), also known as 7α-methylnorethisterone or as 7α-methyl-17α-ethynyl-19-nortestosterone, is a synthetic androgen and progestin which was never marketed.[1][2] The compound is a major active metabolite of tibolone, which itself is a prodrug of δ4-tibolone along with 3α-hydroxytibolone and 3β-hydroxytibolone (which, in contrast to δ4-tibolone, are estrogens).[1] Tibolone and δ4-tibolone are thought to be responsible for the androgenic and progestogenic activity of tibolone, while 3α-hydroxytibolone and 3β-hydroxytibolone are thought to be responsible for its estrogenic activity.[1]

Relative affinities (%) of noretynodrel, tibolone, and metabolites

Compound Code name PR AR ER GR MR SHBG CBG
Noretynodrel 6 0 2 0 0 0 0
  Norethisterone (δ4-NYD) 67–75 15 0 0–1 0–3 16 0
  3α-Hydroxynoretynodrel ? ? ? ? ? ? ?
  3β-Hydroxynoretynodrel ? ? ? ? ? ? ?
  Ethinylestradiol 15–25 1–3 112 1–3 <1 0.18 <0.1
Tibolone (7α-Me-NYD) ORG-OD-14 6 6 1 ? ? ? ?
  Δ4-Tibolone ORG-OM-38 90 35 1 0 2 1 0
  3α-Hydroxytibolone ORG-4094 0 3 4–6 0 ? ? ?
  3β-Hydroxytibolone ORG-301260 0 4 3–29 0 ? ? ?
  7α-Methylethinylestradiol ? ? ? ? ? ? ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR, metribolone for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: See template.

Absolute activities (nM) of tibolone and metabolites

Compound Code name PR AR ERα ERβ GR MR
Tibolone ORG-OD-14 123 1.05 4 105 2410* 170*
Δ4-Tibolone ORG-OM-38 46 0.2 26 300 1760* 30*
3α-Hydroxytibolone ORG-4094 2400* 135* 1.7 100 ND* 1160*
3β-Hydroxytibolone ORG-30126 20000* ND* 2.4 115 ND* 3310*
Notes: Values are affinities (nM). Non-italicized values are EC50. Italicized values with an asterisk (*) are IC50. Reference ligands (EC50) were promegestone (5 nM for PR), metribolone (0.1 nM for AR), estradiol (0.018 nM for ERα, 0.08 nM for ERβ), dexamethasone (6 nM for GR), and aldosterone (0.36 nM for MR). Sources: See template.

See also

References

  1. ^ a b c Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
  2. ^ Escande A, Servant N, Rabenoelina F, Auzou G, Kloosterboer H, Cavaillès V, Balaguer P, Maudelonde T (2009). "Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites". J. Steroid Biochem. Mol. Biol. 116 (1–2): 8–14. doi:10.1016/j.jsbmb.2009.03.008. PMID 19464167.