Methylpiperidino pyrazole is a highly selective estrogen receptor α (Erα) antagonist with an IC50 value of 20.01nM[1]. Methylpiperidino pyrazole binds selectively to ESR1 rather than ESR2 and exhibits both agonistic and antagonistic actions in cultured target cells of uterine origin as well as in the uteri of mice[2]. Methylpiperidino pyrazole also has the ability to attenuate osteoblast maturation[3].
In vitro, MCF-7 cells pretreated with Methylpiperidino pyrazole (100nM) for 30 minutes completely inhibited cell proliferation induced by bisphenol S (BPS) (10μM; 72h) and specifically suppressed the increase of S phase induced by BPS[4]. The treatment of glioblastoma (GBM) cells with Methylpiperidino pyrazole at a concentration of 1μM for a duration of 2 hours effectively blocked the ability of estradiol (E2) to enhance the migration and invasion capabilities of these GBM cells[5].
In vivo, intraperitoneal injection of E2 (0.5μg/gbw) in male adult pompano fish was significantly attenuated in the up-regulation of Erα, estrogen receptors β2 (Erβ2), vitellogenin-B (vtg-B), and vtg-C by Methylpiperidino pyrazole, which also promoted the expressions of erβ1 and vtg-A[6]. Ovariectomized wild-type (WT) and estrogen receptor-β knockout (ERβKO) CF1 mice were treated with Methylpiperidino pyrazole (25, 50, 100, or 150mg; i.p.), which significantly increased uterine weight and cell proliferation[7].
References:
[1] Karaboğa Arslan AK, Yerer MB. α-Chaconine and α-Solanine Inhibit RL95-2 Endometrium Cancer Cell Proliferation by Reducing Expression of Akt (Ser473) and ERα (Ser167). Nutrients. 2018;10(6):672.
[2] Davis AM, Mao J, Naz B, Kohl JA, Rosenfeld CS. Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus. J Mol Endocrinol. 2008;41(4):205-217.
[3] Rodriguez-Merchan, E.C. The importance of smoking in orthopedic surgery. Hosp. Pract. 2018, 46, 175–182.
[4] Lin Z, Zhang X, Zhao F, Ru S. Bisphenol S promotes the cell cycle progression and cell proliferation through ERα-cyclin D-CDK4/6-pRb pathway in MCF-7 breast cancer cells. Toxicol Appl Pharmacol. 2019;366:75-82.
[5] Hernández-Vega AM, Del Moral-Morales A, Zamora-Sánchez CJ, Piña-Medina AG, González-Arenas A, Camacho-Arroyo I. Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells. Cells. 2020;9(9):1930.
[6] Li X, Brighton Ndandala C, Zhou Q, Huang C, Li G, Chen H. Molecular cloning of estrogen receptor and its function on vitellogenesis in pompano (Trachinotus ovatus). Gen Comp Endocrinol. 2024;346:114403.
[7] Davis AM, Ellersieck MR, Grimm KM, Rosenfeld CS. 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. Mol Reprod Dev. 2006;73(8):1034-1044.
Methylpiperidino pyrazole是一种对雌激素受体α（Erα）具有高度选择性的拮抗剂，其半数抑制浓度（IC50）为20.01nM[1]。Methylpiperidino pyrazole选择性地与ESR1而非ESR2结合，并在培养的子宫源性靶细胞以及小鼠子宫中展现出激动剂和拮抗剂的双重作用[2]。Methylpiperidino pyrazole还可以抑制成骨细胞的成熟[3]。
在体外，经Methylpiperidino pyrazole（100nM）预处理30分钟的MCF-7细胞，能够完全抑制双酚S（BPS，10μM；72h）诱导的细胞增殖，并特异性地抑制BPS诱导的S期增加[4]。1μM的Methylpiperidino pyrazole处理2h，可以阻断雌二醇（E2）增加胶质母细胞瘤（GBM）细胞迁移和侵袭的能力[5]。
在体内，成年雄性pompano鱼经腹腔注射E2（0.5μg/gbw）后，Methylpiperidino pyrazole显著抑制了Erα、雌激素受体β2（Erβ2）、卵黄蛋白B（vtg-B）和vtg-C的上调，同时促进了erβ1和vtg-A的表达[6]。对野生型（WT）和雌激素受体β敲除（ERβKO）的去卵巢CF1小鼠进行Methylpiperidino pyrazole（25、50、100或150mg；腹腔注射）处理，显著增加了子宫重量和细胞增殖[7]。