3α-Hydroxytibolone

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
3α-Hydroxytibolone
3α-Hydroxytibolone.svg
Clinical data
SynonymsORG-4094; 7α-Methyl-17α-ethynylestr-5(10)-ene-3α,17β-diol
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC21H30O2
Molar mass314.469 g/mol g·mol−1
3D model (JSmol)

3α-Hydroxytibolone (developmental code name ORG-4094) is a synthetic steroidal estrogen which was never marketed.[1][2] Along with 3β-hydroxytibolone and δ4-tibolone, it is a major active metabolite of tibolone, and 3α-hydroxytibolone and 3β-hydroxytibolone are thought to be responsible for the estrogenic activity of tibolone.[1][2]

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.

References[edit]

  1. ^ a b Kuhl, H (2009). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 (sup1): 3–63. doi:10.1080/13697130500148875. ISSN 1369-7137. PMID 16112947.
  2. ^ a b 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.