Ulipristal acetate targets the progesterone receptor (PR), acting as a selective progesterone receptor modulator with both agonist and antagonist properties. For emergency contraception, its primary mechanism is inhibition or delay of ovulation via suppression of the luteinizing hormone (LH) surge. For uterine fibroids, it exerts a direct action on fibroids, reducing their size through inhibition of cell proliferation and induction of apoptosis. It also stimulates autophagic responses selectively in leiomyoma cells.

In leiomyoma cells, ulipristal acetate (0.1–5 μM; 96 h) promotes autophagy. Ulipristal produced alterations in the expression of the autophagy markers p62/SQSTM1 and LC3. In leiomyoma cells, ulipristal upregulates the Atg7 protein [2]. In cultured uterine fibroids and leiomyoma cells, ulipristalacetate inhibits the regulation of activin A on fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression [4].
In vitro, ulipristal acetate binds to the progesterone receptor with high affinity, inhibiting PR-mediated gene expression. It demonstrates partial agonistic as well as antagonistic effects on the progesterone receptor. In leiomyoma cells, it stimulates autophagic responses and induces apoptosis. It inhibits cell proliferation in uterine fibroid cells and modulates gene expression related to cell cycle regulation and apoptosis. Its effects on the glucocorticoid receptor are minimal compared to its PR activity.

In vivo, ulipristal and CDB-4124 exhibit strong anti-pregnancy properties [5]. In all therapy groups, ulipristal acetate decreased the incidence of adenocarcinoma and breast fibroadenoma. Rats exposed to the highest dose of ulipristal acetate [AUC (0-24h)] were exposed to 67 times the therapeutic dose of 10 mg/day in humans. When ulipristal acetate was administered in doses up to 313 times the therapeutic exposure, mice showed no growth in tumors of any kind. The liver, pituitary, thyroid/parathyroid, and epididymis weight alterations, as well as the smallest entire lobule in male and female mice given a dose of 130 mg/kg/day, were the only findings linked to ulipristal acetate in mice. enlargement of hepatocytes [6]. When compared to the control, ulipristal acetate (1 mg/kg and 5 mg/kg) increased in a dose-dependent way the frequency of pathologist assessment of endometrial thickening. Both secretory differentiation and the frequency of subnuclear and supranuclear vacuole formation somewhat decrease with an increase in ulipristal acetate dosage [7].
In vivo, ulipristal acetate is orally bioavailable and effective for emergency contraception when taken within 120 hours of unprotected intercourse. For uterine fibroids, it reduces fibroid size and improves symptoms such as heavy menstrual bleeding. Its mechanism involves inhibition of ovulation via LH surge suppression and direct effects on fibroid tissue through PR modulation and autophagy induction. Clinical studies have demonstrated its efficacy in both indications, with approval in multiple countries.

In vitro enzyme/receptor binding studies for ulipristal acetate typically involve radioligand binding assays using recombinant human progesterone receptor (PR-A and PR-B) or glucocorticoid receptor. Competitive binding experiments with labeled progesterone or dexamethasone are performed to determine binding affinity (Ki). Transactivation assays in cells transfected with PR expression vectors and reporter genes are used to measure agonist/antagonist activity. Standard protocols involve incubating cells with increasing concentrations of ulipristal and measuring reporter activity (e.g., luciferase) to determine EC50 or IC50 values.

In vitro cellular assays for ulipristal acetate include studies using leiomyoma cells, endometrial cells, or other PR-expressing cell lines. Cells are treated with serial dilutions of the compound, and cell proliferation is assessed by [3H]-thymidine incorporation, BrdU incorporation, or cell counting. Apoptosis is quantified by flow cytometry with Annexin V/PI staining or by measuring caspase activity. Autophagy is assessed by LC3-II accumulation and autophagosome formation using immunoblotting or fluorescence microscopy. PR-mediated gene expression is measured by qRT-PCR or reporter assays.

In vivo animal studies for ulipristal acetate include rodent models of ovulation to assess contraceptive efficacy and models of uterine fibroids (e.g., xenografts or hormone-induced fibroid models) to assess tumor reduction. Animals are treated with ulipristal via oral administration, and endpoints include ovulation rate, fibroid size, histopathology, and hormonal profiles. Standard protocols include dose-response assessment and comparison to vehicle or reference treatments. Pharmacodynamic markers such as PR target gene expression are measured in tissues.

Pharmacokinetic properties of ulipristal acetate include good oral bioavailability. It is rapidly absorbed, with peak plasma concentrations achieved within 1-2 hours. It is highly protein-bound (approximately 98%) and has a half-life of approximately 32 hours, supporting once-daily dosing for fibroid treatment. It is metabolized in the liver primarily via CYP3A4, and its major metabolites are active. Elimination occurs via biliary and renal excretion. Food intake does not significantly affect absorption. Its pharmacokinetics are well-characterized in clinical studies.

Toxicological data for ulipristal acetate indicate that it is generally well-tolerated at therapeutic doses. Common adverse effects include headache, nausea, abdominal pain, and menstrual disturbances. For emergency contraception, a single dose is used, with minimal side effects. For uterine fibroids, longer-term use (up to several months) may be associated with endometrial changes, and monitoring is recommended. Hepatotoxicity has been reported rarely, leading to restrictions on long-term use in some regions. It is contraindicated during pregnancy and in women with severe liver disease.

[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

Ulipristal acetate is a 20-oxosteroid derived from the 17-hydroxyacetylation of (11β,17α)-17-acetyl-11-[4-(dimethylamino)phenyl]-3-oxoestrost-4,9-dien-17-ol (ulipristal). It is a selective progestin receptor modulator and can be used as an emergency contraceptive. It has multiple functions as a contraceptive, progestin, and progestin receptor modulator. It is a 3-oxo-Δ(4)steroid, steroid ester, acetate, 20-oxosteroid, and tertiary amine compound. Its function is related to estradiol.
Ulipristal acetate is an orally bioavailable acetate derivative of ulipristal, a selective progestin receptor modulator with anti-progestin activity. Ulipristal binds to the progestin receptor (PR), thereby inhibiting PR-mediated gene expression and interfering with the activity of progestin in the reproductive system. Therefore, this drug may inhibit the growth of uterine fibroids. In addition, uristat can be used as an emergency contraceptive by inhibiting or delaying ovulation and affecting endometrial tissue. See also: Uristat (containing the active ingredient).

---

Drug Indications
For emergency contraception within 120 hours (5 days) after unprotected sex or contraceptive failure.
Uristat acetate is indicated for the preoperative treatment of moderate to severe uterine fibroids in women of reproductive age, in one course of treatment.
Uristat acetate is indicated for the intermittent treatment of moderate to severe uterine fibroids in women of reproductive age who are not suitable for surgery.
Uristat acetate is indicated for the preoperative treatment of moderate to severe uterine fibroids in women of reproductive age. Uristat acetate is indicated for the intermittent treatment of moderate to severe uterine fibroids in women of reproductive age.
Contraception
Uterine fibroids
Ulipristal acetate is approved for emergency contraception (Ella) in many countries and for the treatment of uterine fibroids (Fibristal) in Europe and Canada. It is a selective progesterone receptor modulator with a unique pharmacological profile. Its dual mechanism—inhibition of ovulation and direct action on fibroids—makes it a valuable therapeutic agent. It is available as an oral tablet and is generally well-tolerated. Research continues into its potential applications in other conditions such as endometriosis and breast cancer. It represents an important advance in women’s health therapeutics.

C30H37NO4

475.6191

475.272

126784-99-4

Ulipristal;159811-51-5;Ulipristal acetate-d6;1621894-64-1

130904

White to off-white solid powder

1.2±0.1 g/cm3

640.1±55.0 °C at 760 mmHg

183-185ºC

340.9±31.5 °C

0.0±1.9 mmHg at 25°C

1.594

4.48

0

5

5

35

984

5

O(C(C([H])([H])[H])=O)[C@]1(C(C([H])([H])[H])=O)C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4=C([H])C(C([H])([H])C([H])([H])C4=C3[C@@]([H])(C3C([H])=C([H])C(=C([H])C=3[H])N(C([H])([H])[H])C([H])([H])[H])C([H])([H])[C@@]21C([H])([H])[H])=O

OOLLAFOLCSJHRE-ZHAKMVSLSA-N

InChI=1S/C30H37NO4/c1-18(32)30(35-19(2)33)15-14-27-25-12-8-21-16-23(34)11-13-24(21)28(25)26(17-29(27,30)3)20-6-9-22(10-7-20)31(4)5/h6-7,9-10,16,25-27H,8,11-15,17H2,1-5H3/t25-,26+,27-,29-,30-/m0/s1

[(8S,11R,13S,14S,17R)-17-acetyl-11-[4-(dimethylamino)phenyl]-13-methyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl] acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~70.08 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)