Methylpiperidino pyrazole

MPP is a highly selective estrogen receptor alpha (ERα) antagonist. MPP reduces the ratio of p-ERα/ERα[1].https://www.ncbi.nlm.nih.gov/pubmed/29799481Labouesse MA, et al. Effects of selective estrogen receptor alpha and beta modulators on prepulse inhibition in male mice. Psychopharmacology (Berl). 2015 Aug;232(16):2981-94.https://www.ncbi.nlm.nih.gov/pubmed/25893642

MPP (1, 5, 10, 25, 50 and 100 µM; 24 h) decreases cell viability with an IC50 value of 20.01 µM in RL95-2 cells[1]. MPP dihydrochloride shows antiproliferative activity at a concentration of 10 μM in RL95-2 cells[1]. MPP dihydrochloride (20 µM; 24 h) reduces the phosphorylation of ERα, while it does not alter the phosphorylation of Akt. MPP dihydrochloride reduces the ratio of p-ERα/ERα[1]. Cell Viability Assay[1] Cell Line: RL95-2 endometrium cancer cells Concentration: 1, 5, 10, 25, 50 and 100 µM Incubation Time: 24 hours Result: The treatment with 25 µM, 50 µM and 100 µM for 24 h decreased cell viability significantly. However, cell viability was not significantly changed by MPP dihydrochloride at concentration below 25 µM. Cell Proliferation Assay[1] Cell Line: RL95-2 cell Concentration: 10, 15, 20 and 25 µM Incubation Time: 72 hours Result: Showed antiproliferative activity at a concentration of 10 μM. Western Blot Analysis[1] Cell Line: RL95-2 cell line Concentration: 20 µM Incubation Time: 24 hours Result: Reduced the phosphorylation of ERα, while it did not alter the phosphorylation of Akt. Reduced the ratio of p-ERα/ERα compared to the control group.

MPP (Low dose 20 μg/kg body weight or high dose 200 μg/kg body weight) leads to a dose-dependent attenuation of percent prepulse inhibition (PPI)[2]. Animal Model: Male C57BL/6N mice at the age of 9-10 weeks[2] Dosage: Low dose (20 μg/kg body weight) or high dose (200 μg/kg body weight) Administration: Administered subcutaneously (s.c.) injected; injection volume of 5 mL/kg; 60 min before PPI testing Result: Led to a dose-dependent attenuation of percent PPI. Pretreatment with 200 μg/kg reduced the mean percent PPI scores by ~30%.

[1]. Karaboğa Arslan AK, et al. α-Chaconine and α-Solanine Inhibit RL95-2 Endometrium Cancer Cell Proliferation by Reducing Expression of Akt (Ser473) and ERα (Ser167). Nutrients. 2018 May 25;10(6). pii: E672.  

[2]. Labouesse MA, et al. Effects of selective estrogen receptor alpha and beta modulators on prepulse inhibition in male mice. Psychopharmacology (Berl). 2015 Aug;232(16):2981-94.