4-[2-Phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol

PHTPP is a pyrazolo[1,5-α]pyrimidine-based ligand that acts as a full antagonist of estrogen ERβ receptors with 36-fold selectivity over ERα. It exhibits no significant agonism on ERα or ERβ. This compound has been used to selectively target ERβ in the study of the opposing effects of hormone therapy on tumors expressing either ER subtype. At 100 pM, PHTPP has been found to enhance SKOV3 and OV2008 ovarian cancer cell growth in in vitro assays.

PHTPP can be used in pharmaceutical combination chemotherapy for treatment of cancer by exploiting estrogen receptor β (ERβ) and TP53 interaction.

ChEBI: 4-[2-phenyl-5,7-bis(trifluoromethyl)-3-pyrazolo[1,5-a]pyrimidinyl]phenol is a member of pyrazoles and a ring assembly.

Selective estrogen ER β receptor antagonist that displays 36-fold selectivity over ER α . Exhibits full antagonism at ER β in a cotransfection assay in human endometrial cancer cells (HEC-1), with minimal effects on ER α .

PHTPP is a selective estrogen receptor β (ERβ) full antagonist with 36-fold selectivity for ERβ over ERα. PHTPP has been used to distinguish the various activites of the two estrogen receptors. Estrogen can have opposite effects in some tumors expressing ERα compared to Erβ, with Erα enhancing and Erβ suppressing tumor cell growth. PHTPP, a selective ERβ antagonist, significantly enhanced cell growth in ovarian cancer cell lines SKOV3 and OV2008 that express both receptors.

Room temperature

[1] DENNIS R. COMPTON. Pyrazolo[1,5-a]pyrimidines: Estrogen Receptor Ligands Possessing Estrogen Receptor β Antagonist Activity.[J]. Journal of Medicinal Chemistry, 2005, 48 7: 2724. DOI: 10.1021/jm058162z
[2] KAREN KAR-LOEN CHAN. Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer.[J]. Journal of Endocrinology, 2014, 221 2: 325-336. DOI: 10.1530/joe-13-0500