1,3-BIS(4-HYDROXYPHENYL)-4-METHYL-5-[4-(2-PIPERIDINYLETHOXY)PHENOL]-1H-PYRAZOLE DIHYDROCHLORIDE

Uses

MPP is a high affinity silent antagonist at ERα.

Biological Activity

Selective, high affinity silent antagonist at ERa receptors. Displays > 200-fold selectivity for ERa over ERb. K i values are 2.7 and 1800 nM at ERa and ERb receptors respectively.

in vitro

mpp elicited significant apoptosis in the endometrial cancer cell lines, rl-95 cells, and ovine luminal endometrial cell lines relative to the vehicle-treated cells. it was indicated that selective estrogen receptor modulators-induced apoptosis is ascribed to genomic actions instead of toxicity, which was due to the low percentage of apoptosis reduced by the addition of a 10-fold excess of β-estradiol [1].

in vivo

wild-type (wt) cf1 and estrogen receptor-β knockout (erbko) female mice were injected intraperitoneally with two dosages 24 hr apart of 100 mg and 150 mg of mpp, 50 mg and 50 mg mpp, respectively. mpp significantly increased uterine weight and cell proliferation when compared to the vehicle control in wt and erbko mice. however, compared to the control groups, mpp did not effectively increase uterine wet weight. mpp treatment of ovariectomized mice activated apoptosis of the underlying uterine stromal cells without triggering apoptosis of the luminal epithelial cells [1].

IC 50

80 nm: blocks the transcriptional activation of the estrogen receptor (er) α.

References

[1]. davis, a., ellersieck, m., grimm, k., & rosenfeld, c. the effects of the selective estrogen receptor modulators, methyl-piperidino-pyrazole (mpp), and raloxifene in normal and cancerous endometrial cell lines and in the murine uterus. molecular reproduction and development. 2006; 73(8): 1034-1044.