Prinaberel is a synthetic, nonsteroidal agonist with high selectivity for estrogen receptor beta (ERβ) over estrogen receptor alpha (ERα). The compound is identified by CAS 524684-52-4 and has the molecular formula C15H10FNO3. The Prinaberel molecular weight is 271.24 g/mol.
Its benzoxazole scaffold carries hydroxy, fluoro, and vinyl substituents arranged for binding within the ERβ ligand pocket. This preference helps distinguish ERβ-dependent effects from ERα-mediated responses.
Application of Prinaberel (ERB-041)
ERB-041 is used to distinguish ERβ-mediated signaling from responses involving ERα or nonselective estrogens. It supports receptor-binding and transcriptional assays, target validation, and comparisons with other subtype-selective ligands.
Researchers also use it to examine inflammation, pain, epithelial biology, and hormone-responsive tissues. Receptor expression, species, tissue, and disease model should be controlled because the observed responses are context dependent.
In Vitro
The receptor-binding profile of the Prinaberel structure shows a reported IC50 of 5.4 nM for human ERβ and approximately 1,200 nM for human ERα. Similar differences were observed in rat and mouse assays, giving more than 200-fold selectivity across the tested species.
In ERβ-expressing cells, Prinaberel repressed selected TNF-α-induced proinflammatory genes. In LPS-activated peritoneal macrophages, it also reduced inducible nitric oxide synthase (iNOS) production together with suppression of NF-κB activation. These responses depend on the cell model and stimulation conditions.
In Vivo
Preclinical studies of Pfizer Prinaberel reported activity in rodent models of arthritis, inflammatory bowel disease, and experimentally induced endometriosis. In UVB-irradiated SKH-1 mice, topical treatment reduced skin tumor burden, proliferation and angiogenesis markers, while increasing apoptosis and reducing WNT/β-catenin signaling.
In a 12-week randomized Phase II study in rheumatoid arthritis, however, prinaberel did not demonstrate a statistically significant improvement over placebo in the primary ACR20 endpoint. This contrast is relevant when evaluating translation from ERβ-focused animal models to patients.
Biochemical and Physiological Actions
The Prinaberel molecular structure occupies the ERβ ligand-binding domain and stabilizes an agonist-compatible conformation. Activated ERβ recruits coregulatory proteins and modifies transcription through estrogen response elements or crosstalk with other pathways. Effects vary with receptor abundance, coregulator availability, and cellular state.
In selected models, anti-inflammatory effects include lower expression of cytokines, iNOS, and other NF-κB-associated mediators. These findings should not be treated as a universal response to ERβ activation.
Features and Benefits of Prinaberel
- Prinaberel chemical structure characterized in an ERβ ligand-binding-domain co-crystal.
- Pfizer reference identifier PF-00913086 for consistent compound documentation.
- More than 200-fold ERβ selectivity over ERα in reported cross-species assays.
- Applicable to binding, transcriptional, inflammation, and tissue-response studies.
- Published preclinical evidence together with an informative negative Phase II outcome.
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