PHTPP

Selective estrogen ERß receptor antagonist

What is PHTPP?

• PHTPP (IUPAC: 4-[2-Phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol) is a synthetic small molecule. Wikipedia

• It is non-steroidal. Wikipedia+1

• It is used for research purposes only, not for therapeutic use in humans.

What is its functionality / mechanism of action?

• PHTPP is a selective antagonist of the estrogen receptor beta (ER β, also written ERβ). Wikipedia+2

• It shows around 36-fold greater selectivity for ERβ over estrogen receptor alpha (ER α/ERα). 

• In functional assays (cotranfection assays in certain cell lines) it exhibits full antagonism of ERβ. 

• In other words: when ERβ is activated by its ligand (e.g., estrogens), PHTPP can bind (or in effect block) so that ERβ cannot carry out its usual transcriptional/regulatory functions. 

Why or where is it used in research?

• Because ERβ and ERα often have different (sometimes opposing) roles in cells, a compound like PHTPP helps researchers dissect out the functions specifically mediated by ERβ. For example:

  • In cancer biology: to understand how ERβ influences proliferation, apoptosis, gene regulation. 

  • In neuroscience / endocrine signalling: to study how estrogen receptor subtypes impact brain, cardiovascular, immune systems. PMC

• For example: in a cell model, PHTPP has been used to block ERβ’s inhibitory effect on tumour cells, thereby causing increased proliferation in that specific context. 

• In animal studies: PHTPP has been used to block the beneficial (anti-fibrotic, anti-inflammatory) effects of ERβ activation in e.g. liver or intestinal models. 

Key details / practical points

• Molecular weight: ~ 423.31 g/mol. 

• Formula: C₍₂₀₎H₍₁₁₎F₆N₃O. 

• CAS Number: 805239-56-9. 

• Solubility: example, soluble up to ~33 mM in DMSO, ~100 mM in ethanol (depending on preparation). 

• Storage / usage: It's a reagent for in-vitro (cell culture) or in-vivo (animal) research. Not approved as a drug. Not for human therapeutic use.

Limitations / considerations

• Just because it is selective (~36-fold) doesn’t mean it is absolutely specific: off-target effects can still occur, particularly at high concentrations or in complex biological systems.

• Antagonising ERβ may produce very different outcomes depending on tissue context, species, ligand environment, etc. i.e., blocking ERβ might have unintended consequences.

• Use in research should rely on proper controls (e.g., ERβ knockdown/knockout, ERα antagonists, other receptor assays) to validate conclusions.

• As with many receptor modulators, dosing, timing, context (cell type, ligand presence, receptor expression levels) matter a lot.

• Because it is a research chemical only, results from PHTPP experiments should be interpreted with caution when extrapolating toward therapeutic or clinical relevance.

0°C (short term), -20°C (long term), desiccated

1) Compton, D.R., Sheng, S., Carlson, K.E., et al. Pyrazolo[1,5-a]pyrimidines: Estrogen receptor ligands possessing estrogen receptor β antagonist activity. J. Med. Chem. 47(24), 5872-5893 (2004).

2) Chan, K.K.L., Leung, T.H.Y., Chan, D.W., et al. Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer. J. Endocrinol. 221(2), 325-336 (2014).