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Purity: ≥98%
Segesterone acetate (formerly known as ST1435; ST-1435 or nestorone; trade name: Annovera) is a progesterone receptor agonist that is prescribed as a female contraceptive. In August 2018, the FDA approved a novel vaginal ring system that uses estradiol and semen to prevent pregnancy for a full year. Segesterone inhibits proinflammatory mediators and neuropathology in the wobbler mouse model of motoneuron degeneration as a female-contraceptive drug. Segesterone may have benefits for multiple sclerosis (MS) as it prevented hippocampal abnormalities and enhanced the functional outcomes of EAE mice.
| Targets |
progesterone receptor (EC50 = 50.3 nM)
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| ln Vivo |
Following Segesterone acetate (400 μCi 3H Nestoron/kg BW; subcutaneous injection; female Sprague-Dawley rats) treatment, the Cmax in plasma and blood is 95.5 and 58.1 ng equiv. 3H Nestoron/g, respectively, with a t1/2 of 15.6 hours. Feces and urine excrete about 81.4% and 7.62% of the dose that was administered, respectively[1].
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Contraceptive vaginal rings provided sustained release of contraceptive levels of segesterone acetate over 90 days in a pharmacokinetic study of healthy women. Following vaginal administration for up to 13 cycles, segesterone acetate was absorbed into systemic administration and reached the peak plasma concentration in 2 hours in Cycle 1, Cycle 3, and Cycle 13. Concentrations declined after time to reach plasma concentration (Tmax) and became more constant after 96 hours post-dose.Over subsequent cycles of use, the peak serum concentrations of segesterone acetate decreased. In Cycle 1, 3 and 13, the peak plasma concentrations were 1147, 363, and 294 pg/mL. In a pharmacokinetic study, approximately 81.4% and 7.62% of the subcutaneously-administered dose in rats was excreted via feces and urine, respectively. The volume of distribution of segesterone acetate is 19.6 L/kg. No pharmacokinetic data available. Metabolism / Metabolites Segesterone acetate undergoes rapid metabolism and inactivation in the liver. Based on the findings _in vitro_, the major oxidative metabolites in the serum include 5α-dihydro- and 17α-hydroxy-5α-dihydro metabolites constitute about 50% of exposure relative to segesterone acetate. The metabolites are not pharmacologically active with EC50 to progesterone receptor 10-fold higher than that of the parent compound. It was shown that 3α, 5α-tetrahydrosegesterone acetate acts as an activator at the GABA-A receptors in the brain. Biological Half-Life The mean (SD) half life of segesterone acetate is 4.5 (3.4) hours. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Based on the available evidence, expert opinion in the United States holds that postpartum women who are breastfeeding should not use combined hormonal contraceptives during the first 3 weeks after delivery because of concerns about increased risk for venous thromboembolism and generally should not use combined hormonal contraceptives during the fourth week postpartum because of concerns about potential effects on breastfeeding performance. Postpartum breastfeeding women with other risk factors for venous thromboembolism generally should not use combined hormonal contraceptives until 6 weeks after delivery. World Health Organization guidelines are more restrictive, stating that combined oral contraceptives should not be used in nursing mothers before 42 days postpartum and the disadvantages of using the method generally outweigh the advantages between 6 weeks and 6 months postpartum. A decrease in milk supply can happen over the first few days of estrogen exposure. ◉ Effects in Breastfed Infants Relevant published information on segesterone acetate and ethinyl estradiol vaginal insert was not found as of the revision date. Studies on the use of segesterone acetate implants have found no adverse effects on growth and development. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Serum protein binding of segesterone acetate is approximately 95% and it displays negligible binding affinity for sex hormone-binding globulin (SHBG). |
| References | |
| Additional Infomation |
Pharmacodynamics
Segesterone acetate suppresses ovulation. In a Phase I randomized, placebo-controlled, randomized crossover study involving healthy adult female subjects, there was no clinically significant QTc interval prolongation following a single intravenous bolus dose of segesterone acetate. Segesterone acetate shows no androgenic, anabolic, or estrogenic activity. It also did not show uterotropic activity in ovariectomized rats. In the endometrial transformation test to assess the progestational activity, dose-dependent increases in both uterine weight was observed following subcutaneous administration of segesterone acetate. |
| Molecular Formula |
C23H30O4
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|---|---|---|
| Molecular Weight |
370.49
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| Exact Mass |
370.214
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| Elemental Analysis |
C, 74.56; H, 8.16; O, 17.27
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| CAS # |
7759-35-5
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| Related CAS # |
7690-08-6;7759-35-5 (acetate);
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| PubChem CID |
108059
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| Appearance |
White to off-white solid powder
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| Density |
1.15g/cm3
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| Boiling Point |
499.3ºC at 760mmHg
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| Melting Point |
173-177
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| Flash Point |
216.2ºC
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| Index of Refraction |
1.549
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| LogP |
4.185
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
762
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC([C@]1(OC(C)=O)[C@@]2([C@]([H])([C@@]3(CCC4=CC(CC[C@@]4([C@]3(CC2)[H])[H])=O)[H])CC1=C)C)=O
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| InChi Key |
CKFBRGLGTWAVLG-GOMYTPFNSA-N
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| InChi Code |
InChI=1S/C23H30O4/c1-13-11-21-20-7-5-16-12-17(26)6-8-18(16)19(20)9-10-22(21,4)23(13,14(2)24)27-15(3)25/h12,18-21H,1,5-11H2,2-4H3/t18-,19+,20+,21-,22-,23-/m0/s1
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| Chemical Name |
[(8R,9S,10R,13S,14S,17R)-17-acetyl-13-methyl-16-methylidene-3-oxo-2,6,7,8,9,10,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 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 (6.75 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6991 mL | 13.4956 mL | 26.9913 mL | |
| 5 mM | 0.5398 mL | 2.6991 mL | 5.3983 mL | |
| 10 mM | 0.2699 mL | 1.3496 mL | 2.6991 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04272008 | Completed | Drug: Segesterone Acetate and Ethinyl Estradiol Other: Tampon |
Contraception | TherapeuticsMD | March 6, 2020 | Phase 1 |
| NCT04290390 | Completed | Drug: Segesterone Acetate and Ethinyl Estradiol Drug: Rifampin |
Women Hemodialysis |
TherapeuticsMD | February 12, 2020 | Phase 1 |
COA
