PHTPP
目录号 : GC11863
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。
Cas No.:805239-56-9
Sample solution is provided at 25 µL, 10mM.
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]。
| Cell experiment [1]: | |
Cell lines | MCF-7 cells |
Preparation Method | MCF-7 cells were cultured in Minimum Essential Medium. All media were supplemented with 10% fetal bovine serum (FBS), penicillin (100U/mL) and streptomycin (100mg/mL). The cells were pre-treated with 5μM selective ERβ full antagonist (PHTPP) for 1h. |
Reaction Conditions | 5μM; 1h |
Applications | PHTPP significantly weakened the inhibitory effect of silibinin on MCF-7 breast cancer cells by blocking the activity of Erβ. |
| Animal experiment [2]: | |
Animal models | Sprague-dawley rat model |
Preparation Method | Ninety female Sprague-Dawley rats, weighing 186±15g with an average age of approximately 8 weeks, were housed in a temperature and humidity-controlled environment with 12h light dark cycles and free access to food and water. The rats were randomly divided as follows into 9 groups of 10 rats each: Control, Carbon tetrachloride (CCl4), CCl4+E2, CCl4+PPT, CCl4+DPN, CCl4+G1, CCl4+E2+MPP, CCl4+E2+PHTPP and CCl4+E2+G15. The Control group underwent sham surgery, while the other 8 groups underwent bilateral ovariectomy. Two weeks after the surgeries, the 8 CCl4 groups were subcutaneously injected with 40% CCl4 in peanut oil at a dose of 0.2mL/100g body weight twice weekly. 5% alcohol was added to drinking water to induce P450 and intensify the development of hepatic fibrosis. Starting from the first CCl4 injection day, the rats received subcutaneously injections of the corresponding drugs (E2, PPT, DPN, G1, MPP, PHTPP and G15; first dissolved in DMSO and then diluted with saline) at a dosage of 30nM/100g body weight/day for 12 weeks, according to the grouping classification. The Control and CCl4 groups were treated subcutaneously with the same volume of placebos (peanut oil and/or DMSO diluted with saline). |
Dosage form | 0.091mg/kg; sc; 12 weeks |
Applications | PHTPP could block the antifibrotic effects of E2. |
References: | |
| Cas No. | 805239-56-9 | SDF | |
| 化学名 | 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl)phenol | ||
| Canonical SMILES | FC(F)(C1=CC(C(F)(F)F)=NC2=C(C(C=C3)=CC=C3O)C(C4=CC=CC=C4)=NN21)F | ||
| 分子式 | C20H11F6N3O | 分子量 | 423.31 |
| 溶解度 | ≤30mg/ml in ethanol;50mg/ml in DMSO | 储存条件 | Store at RT |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3623 mL | 11.8117 mL | 23.6233 mL |
| 5 mM | 0.4725 mL | 2.3623 mL | 4.7247 mL |
| 10 mM | 0.2362 mL | 1.1812 mL | 2.3623 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Quality Control & SDS
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- Purity: >99.50%
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