生物活性

Ulipristal acetate (CDB-2914) is an orally active, selective progesterone receptor modulator (SPRM). Ulipristal acetate stimulates the autophagic response selectively in leiomyoma cells. Ulipristal acetate has the potential for benign gynecological conditions treatment, such as uterine myoma^[1][2].

体外研究
(In Vitro)

Ulipristal acetate (0.1-5 μM; 96 hours) stimulates autophagy in leiomyoma cells. Ulipristal-induced expression changes of the autophagic markers LC3 and p62/SQSTM1. Ulipristal up-regulates Atg7 protein in leiomyoma cells^[2].
Ulipristal acetate blocks activin A modulation of fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression in cultured myometrial and leiomyoma cells^[4].

体内研究
(In Vivo)

Ulipristal and CDB-4124 have significant antiprogestational activity in vivo^[5].
Ulipristal acetate decreases incidences of fibroadenomas and adenocarcinomas in the mammary gland in all treated groups. Ulipristal acetate exposure [AUC(0-24h)] at the highest dose in rats is 67 times human therapeutic exposure at 10 mg/day. In mice, no tumor of any type increases at Ulipristal acetate exposures up to 313 times of therapeutic exposure. Ulipristal acetate-related findings in mice are limited to organ weight changes in the liver, pituitary, thyroid/parathyroid glands, and epididymis as well as minimal panlobular hepatocellular hypertrophy in male and female mice receiving 130 mg/kg/day^[6].
Ulipristal acetate (1 mg/kg and 5 mg/kg) increases the frequency with which pathologists assessed the endometrium as being thickened compared to controls in a dose-dependent manner. There is a slight decrease in secretory differentiation with increasing dose of Ulipristal acetate, with small decreases in frequency of sub- and supra-nuclear vacuolation^[7].

Clinical Trial

分子量

475.62

Formula

C??H??NO?

CAS 号

126784-99-4

中文名称

醋酸乌利司他

SMILES

O=C1CCC2=C3[C@@H](C4=CC=C(N(C)C)C=C4)C[C@@]5(C)[C@](CC[C@]5(OC(C)=O)C(C)=O)([H])[C@]3([H])CCC2=C1

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

溶解性数据

In Vitro: 

DMSO : 33.33 mg/mL (70.08 mM; Need ultrasonic)

配制储备液

*

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, 6 months; -20°C, 1 month。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.5 mg/mL (5.26 mM); Clear solution

2.请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.5 mg/mL (5.26 mM); Clear solution

参考文献

[1]. Jadav SP, et al. Ulipristal acetate, a progesterone receptor modulator for emergency contraception. J Pharmacol Pharmacother. 2012 Apr;3(2):109-11.

[2]. Del Bello B, et al. Autophagy up-regulation by ulipristal acetate as a novel target mechanism in the treatment of uterine leiomyoma: an in vitro study. Fertil Steril. 2019 Dec;112(6):1150-1159.

[3]. Hild SA, et al. CDB-2914: anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits. Hum Reprod. 2000 Apr;15(4):822-9.

[4]. Ciarmela P, et al. Ulipristal acetate modulates the expression and functions of activin a in leiomyoma cells. Reprod Sci. 2014 Sep;21(9):1120-5.

[5]. Attardi BJ, et al. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol.

[6]. Pohl O, et al. Carcinogenicity and chronic rodent toxicity of the selective progesterone receptor modulator ulipristal acetate. Curr Drug Saf. 2013 Apr;8(2):77-97.

[7]. Pohl O, et al. A 39-week oral toxicity study of ulipristal acetate in cynomolgus monkeys. Regul Toxicol Pharmacol. 2013 Jun;66(1):6-12.