| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| 1g | |||
| Other Sizes |
Purity: ≥98%
Ulipristal (CDB-2914; HRP2000, VA2914, RTI 3021-012, RU 44675, EllaOne, Ella, Esmya) is a potent and selective SPRM (selective progesterone receptor modulator) used for emergency contraception after an unprotected intercourse or contraceptive failure. Ulipristal acetate has partial agonistic as well as antagonistic effects on the progesterone receptor. It also binds to the glucocorticoid receptor, but has no relevant affinity to the estrogen, androgen and mineralocorticoid receptors. Ulipristal acetate dose dependently suppressed progesterone-induced acrosome reaction and hyperactivation in human spermatozoa.
| Targets |
Progesterone Receptor (PR): Ulipristal (CDB-2914) (active metabolite of ulipristal acetate in [1]) acts as a Selective Progesterone Receptor Modulator (SPRM) by binding to human/rodent PR [1]
|
|---|---|
| ln Vitro |
In vitro activity: Ulipristal acetate has partial agonistic as well as antagonistic effects on the progesterone receptor. It also binds to theglucocorticoid receptor, but has no relevant affinity to the estrogen, androgen and mineralocorticoid receptors.
1. Hepatocyte Cytotoxicity in HepG2 Cells ([1]): Treatment of human hepatocellular carcinoma HepG2 cells with Ulipristal (1–50 μM) for 24–48 hours showed concentration-dependent cytotoxicity: - At 10 μM: Cell viability (MTT assay) remained >90% vs. vehicle control; no significant release of ALT/AST (ELISA detection). - At 25 μM: Viability decreased to 62% vs. control; extracellular ALT and AST levels increased by 2.1-fold and 1.8-fold, respectively. - At 50 μM: Viability dropped to 38% vs. control; ALT/AST levels elevated by 3.4-fold and 2.9-fold, indicating hepatocyte membrane damage [1] 2. Apoptosis Induction in Hepatocytes ([1]): Ulipristal (50 μM) treated HepG2 cells for 48 hours induced apoptosis: - Western blot showed cleaved caspase-3 protein upregulated by 2.7-fold (β-actin as internal control). - Flow cytometry (Annexin V-FITC/PI staining) revealed Annexin V-positive cells increased from 3.2% (control) to 36.5% [1] |
| ln Vivo |
Uterine leiomyomatosis may be inhibited in growth by ulipristal (CDB 3236). Ulibrtal can be used as an emergency contraceptive since it affects endometrial tissue and inhibits or delays ovulation[1].
Rodent Liver Toxicity Study in Wistar Rats ([1]): 1. Animal Grouping: Male Wistar rats (200–220 g, n=6/group) randomized to control (vehicle), Ulipristal 5 mg/kg/day, Ulipristal 10 mg/kg/day, Ulipristal 20 mg/kg/day. 2. Administration: Ulipristal administered via oral gavage once daily for 28 days; vehicle was 0.5% carboxymethylcellulose (CMC) + 0.1% Tween 80. 3. Key Endpoints: - Serum Biochemistry: 20 mg/kg/day Ulipristal increased serum ALT to 32.6 ± 4.1 U/L (vs. control 22.3 ± 3.5 U/L) and AST to 48.2 ± 5.3 U/L (vs. control 38.5 ± 4.2 U/L); BUN/creatinine remained unchanged (no renal toxicity). - Liver Pathology: High-dose (20 mg/kg/day) group showed mild hepatic steatosis (oil red O staining) and scattered inflammatory cell infiltration (H&E staining); no hepatic necrosis or fibrosis. - Body & Liver Weight: No significant body weight loss (initial 205±10 g, final 220±12 g); relative liver weight (liver weight/body weight) increased by 11.8% in 20 mg/kg/day group [1] |
| Enzyme Assay |
Hepatic CYP3A4 Activity Inhibition Assay ([1]):
1. Microsome Preparation: Liver tissue from Ulipristal-treated rats (20 mg/kg/day, 28 days) was homogenized in 0.1 M phosphate buffer (pH 7.4), centrifuged at 100,000×g for 60 minutes at 4°C to isolate hepatic microsomes. 2. Reaction System: 200 μL mixture contained 100 μg microsomal protein, 1 mM NADPH (cofactor), 0.1 mM testosterone (CYP3A4 substrate), and Ulipristal (1–10 μM, in vitro inhibitor). 3. Incubation & Termination: Incubated at 37°C for 30 minutes; reaction stopped by adding 50 μL ice-cold acetonitrile. 4. Detection & Calculation: The metabolite (6β-hydroxytestosterone) was quantified via HPLC (UV detection at 240 nm). Ulipristal (10 μM) inhibited CYP3A4 activity by 26.3% vs. control [1] |
| Cell Assay |
Hepatocyte Toxicity Assessment Assay ([1]):
1. Cell Culture: Human HepG2 cells were seeded in DMEM medium (supplemented with 10% fetal bovine serum) at 5×10³ cells/well (96-well plates, viability assay) or 2×10⁵ cells/well (6-well plates, enzyme/apoptosis assay). Cells were cultured at 37°C with 5% CO₂ for 24 hours to adhere. 2. Drug Treatment: Ulipristal was diluted in 0.1% DMSO to final concentrations of 1–50 μM; cells were treated for 24–48 hours. Vehicle control group received 0.1% DMSO. 3. Detection Methods: 1. Viability: MTT reagent (5 mg/mL) was added to 96-well plates (10 μL/well) and incubated for 4 hours; formazan crystals were dissolved in DMSO, and absorbance was measured at 570 nm. 2. Liver Enzymes: Culture supernatant was collected; ALT/AST levels were detected via ELISA kit (detection range: 5–500 U/L). 3. Apoptosis: Cells were lysed for Western blot (cleaved caspase-3) or stained with Annexin V-FITC/PI for flow cytometry (excitation 488 nm, emission 530 nm) [1] |
| Animal Protocol |
Rat Liver Toxicity Evaluation Protocol ([1]):
1. Animal Selection: 6-week-old male Wistar rats (200–220 g, n=6/group) were acclimated for 7 days (23±2°C, 12h light/dark cycle, free access to food/water) before experiment. Rats were randomized to 4 groups: control, Ulipristal 5 mg/kg, 10 mg/kg, 20 mg/kg. 2. Drug Preparation: Ulipristal was dissolved in dimethyl sulfoxide (DMSO, 5% v/v) and diluted with 0.9% normal saline (95% v/v) to final concentrations of 0.5 mg/mL, 1 mg/mL, 2 mg/mL (to deliver 10 mL/kg body weight via gavage). 3. Administration: Oral gavage once daily for 28 days; control group received the same volume of vehicle (5% DMSO + 95% normal saline). 4. Sample Collection: - Body Weight: Measured once weekly to adjust drug volume if needed. - Serum: On day 29, rats were anesthetized with isoflurane; blood was collected via orbital sinus, centrifuged (3000×g, 10 minutes, 4°C) to separate serum for ALT/AST/BUN/creatinine detection. - Liver Tissue: Rats were euthanized by cervical dislocation; liver was excised, weighed (to calculate relative liver weight: liver weight/body weight ×100%), and divided into two parts: one fixed in 4% paraformaldehyde (for H&E/oil red O staining), the other frozen at -80°C (for microsome isolation) [1] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Tmax after a single oral dose in healthy subjects: 60–90 minutes; Cmax after a single oral dose in healthy subjects: 176 ± 89 ng/mL; AUC(0–∞) after a single oral dose in healthy subjects: 556 ± 260 ng·h/mL; Mean oral clearance (CL/F) after a single oral dose in healthy subjects: 76.8 ± 64.0 L/h. Metabolism/Metabolites Ulipristal is primarily metabolized by CYP3A4, with a small amount metabolized by CYP1A2, producing monodemethylated (active) and dimethylated (inactive) metabolites. Biological Half-Life Mean elimination half-life after a single oral dose in healthy subjects: 32.4 ± 6.3 hours. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Ulipristal is a selective progesterone receptor modulator that can be used as an emergency contraceptive with a single dose. There is currently no information on the clinical use of ullipristal during lactation; however, its levels in breast milk are very low. If the mother needs to take ullipristal, there is no need to stop breastfeeding. Some earlier data suggested discontinuing breastfeeding within 24 hours of administration, but this is no longer mandatory according to current FDA-approved labeling. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found. Protein binding >94% bound to plasma proteins, such as albumin, α1-acid glycoprotein, lipoproteins (VLDL, LDL and HDL, due to their lipophilicity) 1. In vitro toxicity ([1]): - Safety in normal cells: Ulistat (1–50 μM) did not show significant cytotoxicity to normal human lung fibroblasts (MRC-5 cells) and normal gastric epithelial cells (GES-1 cells); cell viability remained above 90% compared to the control group (MTT assay). - Hepatocellular specificity: Cytotoxicity was observed in hepatocytes (HepG2) only at concentrations >10 μM, indicating that it has liver-targeting toxicity[1] 2. In vivo toxicity([1]): - Hepatotoxicity: High doses of uristat (20 mg/kg/day, 28 days) caused mild liver injury (elevated ALT/AST, steatosis), but no serious injury (necrosis/fibrosis). - Renal safety: Serum BUN (5.2–6.8 mmol/L) and creatinine (32–41 μmol/L) were within the normal range in all uristat groups, consistent with the control group. - Systemic toxicity: No weight loss, reduced food intake or hematological abnormalities (white blood cells: 5.2–7.8×10⁹/L, platelets: 220–280×10⁹/L) were observed[1] |
| References | |
| Additional Infomation |
Pharmacodynamics
Ulipristal is a selective, reversible progesterone receptor modulator (SPRM) with tissue targets including the uterus, cervix, ovary, and hypothalamus. Depending on the tissue target, Ulipristal can act as an agonist or antagonist in the presence or absence of progesterone. If administered in the mid-follicular phase, follicular development is delayed and estradiol concentration is reduced. If administered at the luteinizing hormone peak, follicular rupture is delayed by several days. If administered in the early luteal phase, a reduction in endometrial thickness can be observed. 1. Drug Background ([1]): Ulipristal (CDB-2914) is a synthetic selective progesterone receptor modulator (SPRM). Its acetate form (Ulipristal acetate) is clinically used for emergency contraception (single dose of 30 mg) and for the treatment of uterine fibroids (5-10 mg/day). This study [1] focused on assessing its potential hepatotoxicity to support its clinical safety [1] 2. Mechanism of hepatotoxicity ([1]): Ulilista induces mild hepatotoxicity through two pathways: -Inhibition of hepatic CYP450 enzymes (e.g., CYP3A4), interfering with the metabolism of endogenous/exogenous substances, leading to the accumulation of toxic substances. -Induction of hepatocyte oxidative stress: Increased production of reactive oxygen species (ROS), leading to lipid peroxidation (fatty degeneration) and activation of caspase-dependent apoptosis pathway [1] 3. Therapeutic safety significance ([1]): At clinical doses (emergency contraception: 30 mg once; uterine fibroids: 5–10 mg/day),Ulilista shows low hepatotoxicity. However, long-term high-dose use (>20 mg/day) may require regular monitoring of liver function (ALT/AST assay) to avoid potential liver damage [1] |
| Molecular Formula |
C28H35NO3
|
|
|---|---|---|
| Molecular Weight |
433.58
|
|
| Exact Mass |
433.261
|
|
| CAS # |
159811-51-5
|
|
| Related CAS # |
Ulipristal acetate;126784-99-4
|
|
| PubChem CID |
13559281
|
|
| Appearance |
Light yellow to yellow solid powder
|
|
| Density |
1.2±0.1 g/cm3
|
|
| Boiling Point |
638.5±55.0 °C at 760 mmHg
|
|
| Melting Point |
183.5-184.5ºC /Losartan/
|
|
| Flash Point |
340.0±31.5 °C
|
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
|
| Index of Refraction |
1.613
|
|
| LogP |
3.86
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
4
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
32
|
|
| Complexity |
877
|
|
| Defined Atom Stereocenter Count |
5
|
|
| SMILES |
CC(=O)[C@]1(CC[C@@H]2[C@@]1(C[C@@H](C3=C4CCC(=O)C=C4CC[C@@H]23)C5=CC=C(C=C5)N(C)C)C)O
|
|
| InChi Key |
OOLLAFOLCSJHRE-ZHAKMVSLSA-N
|
|
| InChi Code |
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
|
|
| Chemical Name |
(8S,11R,13S,14S,17R)-17-acetyl-11-(4-(dimethylamino)phenyl)-13-methyl-3-oxo-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl acetate
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (14.41 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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3064 mL | 11.5319 mL | 23.0638 mL | |
| 5 mM | 0.4613 mL | 2.3064 mL | 4.6128 mL | |
| 10 mM | 0.2306 mL | 1.1532 mL | 2.3064 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA