Selective and potent agonists for estrogen receptor beta derived from molecular refinements of salicylaldoximes.
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Bertini S, De Cupertinis A, Granchi C, Bargagli B, Tuccinardi T, Martinelli A, Macchia M, Gunther JR, Carlson KE, Katzenellenbogen JA, Minutolo F
Selective and potent agonists for estrogen receptor beta derived from molecular refinements of salicylaldoximes.
Eur J Med Chem. 2011 Jun;46(6):2453-62. doi: 10.1016/j.ejmech.2011.03.030. Epub 2011 Mar 23.
- PubMed ID
- 21481497 [ View in PubMed]
- Abstract
In a continuing effort to improve the subtype selectivity and agonist potency of estrogen receptor beta (ERbeta) ligands, we have designed and developed a thus far unexplored structural series obtained by molecular refinements of monoaryl-substituted salicylaldoximes (Salaldox B). The most interesting compounds in this series (2c, d) show remarkably high ERbeta-binding affinities, with Ki values reaching the sub-nanomolar range (Ki=0.38 nM for 2c and 0.57 nM for 2d), and have very high levels of ERbeta-subtype selectivity. Both compounds show a potent full agonist character on ERbeta (EC50=0.23 nM for 2c and 1.3 nM for 2d). Furthermore, 2d shows a remarkable functional subtype selectivity, with a beta/alpha transcription potency ratio 50-fold higher than that of estradiol.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Estradiol Estrogen receptor alpha Kd (nM) 0.2 N/A N/A Details Estradiol Estrogen receptor alpha EC 50 (nM) 0.09 N/A N/A Details Estradiol Estrogen receptor beta Kd (nM) 0.5 N/A N/A Details Estradiol Estrogen receptor beta EC 50 (nM) 0.72 N/A N/A Details