4-Fluoroestradiol

Not to be confused with 16α-Fluoroestradiol.
4-Fluoroestradiol
Clinical data
Other names4-FE2; 4-F-17β-E2; 4-Fluoro-17β-estradiol; 4-Fluoroestra-1,3,5-(10)-triene-3,17β-diol; NSC-94528
Drug classEstrogen
Identifiers
  • (8R,9S,13S,14S,17S)-4-fluoro-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H23FO2
Molar mass290.378 g·mol−1
3D model (JSmol)
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4F)O
  • InChI=1S/C18H23FO2/c1-18-9-8-11-10-4-6-15(20)17(19)13(10)3-2-12(11)14(18)5-7-16(18)21/h4,6,11-12,14,16,20-21H,2-3,5,7-9H2,1H3/t11-,12-,14+,16+,18+/m1/s1
  • Key:QZFXMXJXAUMHQR-ZHIYBZGJSA-N

4-Fluoroestradiol (4-FE2) is a synthetic estrogen and a derivative of estradiol which was never marketed.[1] It is specifically the 4-fluoro analogue of estradiol.[1] 4-Fluoroestradiol has 180 ± 43% of the affinity of estradiol for the estrogen receptor of rat uterine cytosol and shows potent uterotrophic activity similar to that of estradiol in mice and rats.[1][2] It has been labeled with fluorine-18 (18F) for potential use in medical imaging.[3][4][5]

Selected biological properties of endogenous estrogens in rats
Estrogen ERTooltip Estrogen receptor RBATooltip relative binding affinity (%) Uterine weight (%) Uterotrophy LHTooltip Luteinizing hormone levels (%) SHBGTooltip Sex hormone-binding globulin RBATooltip relative binding affinity (%)
Control – 100 – 100 –
Estradiol (E2) 100 506 ± 20 +++ 12–19 100
Estrone (E1) 11 ± 8 490 ± 22 +++ ? 20
Estriol (E3) 10 ± 4 468 ± 30 +++ 8–18 3
Estetrol (E4) 0.5 ± 0.2 ? Inactive ? 1
17α-Estradiol 4.2 ± 0.8 ? ? ? ?
2-Hydroxyestradiol 24 ± 7 285 ± 8 +b 31–61 28
2-Methoxyestradiol 0.05 ± 0.04 101 Inactive ? 130
4-Hydroxyestradiol 45 ± 12 ? ? ? ?
4-Methoxyestradiol 1.3 ± 0.2 260 ++ ? 9
4-Fluoroestradiola 180 ± 43 ? +++ ? ?
2-Hydroxyestrone 1.9 ± 0.8 130 ± 9 Inactive 110–142 8
2-Methoxyestrone 0.01 ± 0.00 103 ± 7 Inactive 95–100 120
4-Hydroxyestrone 11 ± 4 351 ++ 21–50 35
4-Methoxyestrone 0.13 ± 0.04 338 ++ 65–92 12
16α-Hydroxyestrone 2.8 ± 1.0 552 ± 42 +++ 7–24 <0.5
2-Hydroxyestriol 0.9 ± 0.3 302 +b ? ?
2-Methoxyestriol 0.01 ± 0.00 ? Inactive ? 4
Notes: Values are mean ± SD or range. ER RBA = Relative binding affinity to estrogen receptors of rat uterine cytosol. Uterine weight = Percentage change in uterine wet weight of ovariectomized rats after 72 hours with continuous administration of 1 μg/hour via subcutaneously implanted osmotic pumps. LH levels = Luteinizing hormone levels relative to baseline of ovariectomized rats after 24 to 72 hours of continuous administration via subcutaneous implant. Footnotes: a = Synthetic (i.e., not endogenous). b = Atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). Sources: See template.
  1. ^ a b c Martucci CP (July 1983). "The role of 2-methoxyestrone in estrogen action". Journal of Steroid Biochemistry. 19 (1B): 635–638. doi:10.1016/0022-4731(83)90229-7. PMID 6310247.
  2. ^ Longcope C, Rafkind I, Arunachalam T, Caspi E (September 1983). "Biological activities of 4-fluoro estrogen analogues". Journal of Steroid Biochemistry. 19 (3): 1325–1328. doi:10.1016/0022-4731(83)90158-9. PMID 6621038.
  3. ^ Eakins MN, Palmer AJ, Waters SL (November 1979). "Studies in the rat with 18F-4-fluoro-oestradiol and 18F-4-fluoro-oestrone as potential prostate scanning agents: comparison with 125I-2-iodo-oestradiol and 125I-2,4-di-iodo-oestradiol". The International Journal of Applied Radiation and Isotopes. 30 (11): 695–700. doi:10.1016/0020-708x(79)90111-x. PMID 544526.
  4. ^ Cummins CH (June 1993). "Radiolabeled steroidal estrogens in cancer research". Steroids. 58 (6): 245–259. doi:10.1016/0039-128x(93)90069-y. PMID 8212070. S2CID 29080385.
  5. ^ Al Jasem Y, Thiemann T, Gano L, Oliveira MC (2016). "Fluorinated steroids and their derivatives". Journal of Fluorine Chemistry. 185: 48–85. doi:10.1016/j.jfluchem.2016.03.009. ISSN 0022-1139.