PHTPP is a selective ERβ full antagonist with 36-fold selectivity for ERβ over ERα. PHTPP can selectively antagonize the ligand binding and transcriptional functions of ERβ, blocking its inhibitory effect on tumor cells, thereby promoting cell proliferation. PHTPP was used to verify ERβ function [1-3].
In MCF-7 cells, PHTPP (5μM, 1h) significantly weakened the inhibitory effect of silibinin on MCF-7 breast cancer cells by blocking the activity of ERβ [4]. In Caco-2 cells, PHTPP (0.1μM, 24h) reversed the p-hydroxybenzoic acid-induced inhibition of the expression of proinflammatory factors (e.g., TNF-α and IL-6) and upregulated the expression of E-cadherin and occluding [5]. In SKOV3 cells, PHTPP (10μM, 24h) promotes the proliferation and migration of SKOV3 cells [6].
In colitis mouse model, PHTPP (1mg/kg, ip, 1d) reversed the improvement effect of p-hydroxybenzoic acid on the symptoms of colitis [5]. In sprague-dawley rat model, PHTPP (0.091mg/kg, sc, 12 weeks) could block the antifibrotic effects of E2 [7]. In sprague-dawley rat model, PHTPP (850μg/kg, ip, 12d) inhibited ERβ activation by E2 and naringenin by over 90% [8].
References:
[1]. Compton DR, Sheng S, Carlson KE, et al. Pyrazolo [1, 5-a] pyrimidines: estrogen receptor ligands possessing estrogen receptor β antagonist activity. Journal of medicinal chemistry. 2004 Nov 18; 47(24): 5872-5893.
[2]. Chan KK, Leung TH, Chan DW, et al. Targeting estrogen receptor subtypes (ERa and ERb) with selective ER modulators in ovarian cancer. J. Endocrinol. 2014; 221: 325-336.
[3]. Boopathy GT, Hong W. Role of hippo pathway-YAP/TAZ signaling in angiogenesis. Frontiers in cell and developmental biology. 2019 Apr 10; 7: 49.
[4]. Zheng N, Liu L, Liu W, et al. ERβ up-regulation was involved in silibinin-induced growth inhibition of human breast cancer MCF-7 cells. Archives of biochemistry and biophysics. 2016 Feb 1; 591: 141-149.
[5]. Xu X, Luo A, Lu X, et al. p-Hydroxybenzoic acid alleviates inflammatory responses and intestinal mucosal damage in DSS-induced colitis by activating ERβ signaling. Journal of Functional Foods. 2021 Dec 1; 87: 104835.
[6]. Yan Y, Jiang X, Zhao Y, et al. Role of GPER on proliferation, migration and invasion in ligand‐independent manner in human ovarian cancer cell line SKOV3. Cell biochemistry and function. 2015 Dec; 33(8): 552-559.
[7]. Zhang B, Zhang CG, Ji LH, et al. Estrogen receptor β selective agonist ameliorates liver cirrhosis in rats by inhibiting the activation and proliferation of hepatic stellate cells. Journal of Gastroenterology and Hepatology. 2018 Mar; 33(3): 747-755.
[8]. Lin P, Zhang X, Zhu B, et al. Naringenin protects pancreatic β cells in diabetic rat through activation of estrogen receptor β. European Journal of Pharmacology. 2023 Dec 5; 960: 176115.
PHTPP是一种选择性ERβ完全拮抗剂，对ERβ的选择性是ERα的36倍。PHTPP可以选择性拮抗ERβ的配体结合和转录功能，阻断其对肿瘤细胞的抑制作用，从而促进细胞增殖。PHTPP被用于验证ERβ的功能 [1-3]。
在MCF-7细胞中，PHTPP（5μM，1h）通过阻断ERβ的活性显著减弱了水飞蓟宾对MCF-7乳腺癌细胞的抑制作用 [4]。在Caco-2细胞中，PHTPP（0.1μM，24h）逆转了对羟基苯甲酸诱导的促炎因子（例如TNF-α和IL-6）表达的抑制，并上调了 E-钙粘蛋白和闭塞蛋白的表达 [5]。在SKOV3细胞中，PHTPP（10μM，24h）促进SKOV3细胞增殖和迁移 [6]。
在小鼠结肠炎模型中，PHTPP（1mg/kg，ip，1d）可逆转对羟基苯甲酸对结肠炎症状的改善作用 [5]。在Sprague-Dawley大鼠模型中，PHTPP（0.091mg/kg，sc，12周）可阻断E2的抗纤维化作用 [7]。在Sprague-Dawley大鼠模型中，PHTPP（850μg/kg，ip，12d）可抑制E2和柚皮素对ERβ的激活，抑制率达90%以上 [8]。