Gestodene
Based on 1 Customer Validation
Gestodene (SHB 331; WL 70) is an orally active synthetic progestogen compound of the 19-nortestosterone class. Gestodene binds with high affinity to the progesterone receptor, inhibits 5α-reductase, binds to androgen and aldosterone receptors, and inactivates CYP3A. Gestodene acts as a positive allosteric modulator of PAR1, enhances PAR1-mediated signaling pathways, and is capable of increasing the activation potency of PAR1-AP toward PAR1, thereby promoting ERK1/2 phosphorylation, receptor internalization, cell morphological changes, and human platelet aggregation. Gestodene and its A-ring reduced metabolites promote the proliferation, differentiation, and mineralization of neonatal rat osteoblasts. Gestodene itself has no binding capacity for estrogen receptors, and this osteogenic activity depends on intracellular metabolism to generate A-ring reduced products with estrogen-like agonistic activity. Gestodene is useful for research on diseases related to progesterone secretion and diseases related to thrombosis.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 99.89%
- CAS No.: 60282-87-3
- Formule: C21H26O2
- Masse moléculaire:310.43
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Stockage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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HY-B0111
DrospirenoneProgesterone Receptor Agonist -
HY-B0257
LevonorgestrelProgesterone Inhibitor -
HY-B0216
EthinylestradiolEndogenous Metabolite -
HY-B0084
DienogestProgesterone Receptor Agonist -
HY-13636
FulvestrantEstrogen Receptor Antagonist -
HY-16508
Ulipristal acetateSelective Progesterone Receptor Modulator -
HY-B0554
NorethindroneProgestin -
HY-B0151
PregnenoloneCB1 Inhibitor -
HY-12516
DesogestrelProgesterone Receptor Agonist -
HY-A0285
Norethisterone enanthateParenteral Progestogen -
HY-B0652
EtonogestrelProgesterone/ERR Agonist -
HY-13604
Cyproterone acetateAndrogen Receptor Antagonist
Activité biologique
Description
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ERK1 |
ERK2 |
MMP-1 |
MMP-2 |
MMP-3 |
MMP-10 |
CYP3A |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| HT-29 | EC50 |
8.15 μM
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Potency of gestodene to enhance PAR1-AP-induced intracellular calcium increase in human HT29 cells pre-incubated for 10 min and measured by Fluo-4 NW calcium assay.
Potency of gestodene to enhance PAR1-AP-induced intracellular calcium increase in human HT29 cells pre-incubated for 10 min and measured by Fluo-4 NW calcium assay.
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39130626 |
| HT-29 | EC50 |
4.54 μM
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Potency of gestodene to enhance thrombin-induced intracellular calcium increase in human HT29 cells pre-incubated for 10 min and measured by Fluo-4 NW calcium assay.
Potency of gestodene to enhance thrombin-induced intracellular calcium increase in human HT29 cells pre-incubated for 10 min and measured by Fluo-4 NW calcium assay.
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39130626 |
In Vitro
Gestodene inhibits the hydroxylation of ethinyl estradiol in a concentration-dependent manner in human liver microsomes and also inhibits the oxidative metabolism of Cyclosporine and Diazepam[1].
Gestodene (GDN) (1-500 nM; 1-25 days) stimulates the proliferation of neonatal rat calvarial osteoblasts, increases alkaline phosphatase activity in neonatal rat calvarial osteoblasts, and increases cell-associated osteocalcin content in neonatal rat calvarial osteoblasts; the 5α-reductase inhibitor Finasteride (HY-13635) and the aldosterone ketosteroid dehydrogenase inhibitor Flufenamic acid (HY-B1221) inhibit the Gestodene-induced increase in alkaline phosphatase activity[2].
Gestodene (50-500 nM; 25 days) increases cell-associated calcium content in neonatal rat calvarial osteoblasts[2].
Gestodene (1-250 nM; 18 h) shows no binding affinity for estrogen receptors in the cytosolic fraction of neonatal rat calvarial osteoblasts[2].
Gestodene is extensively metabolized to A-ring reduced derivatives (5α gestodene, 3α,5α gestodene, and 3β,5α gestodene) in rat anterior pituitary, hypothalamus, and ventral prostate homogenates[3].
Gestodene (3 μM; 3 days; 4-16 h; 30 min) enhances PAR1-AP-induced proliferation, migration, and ERK1/2 phosphorylation in A2058 cells, HaCaT cells, and HDF cells in a PAR1-dependent manner; this enhancing effect is blocked by Vorapaxar (HY-10119)[4].
Gestodene acts as a positive allosteric modulator of PAR1 in HT29 cells, enhancing PAR1-AP- and thrombin-induced intracellular calcium levels with EC50 values of 8.15 μM and 4.54 μM, respectively, without affecting PAR2 or PAR4 activity[5].
Gestodene (10 μM) enhances PAR1-AP-induced intracellular calcium levels in MEG-01 cells, reducing the EC50 of PAR1-AP from 6.58 μM to 3.41 μM[5].
Gestodene (10 μM; 10 min) enhances PAR1-AP-induced ERK1/2 phosphorylation in MEG-01 cells through a PAR1-dependent mechanism[5].
Gestodene (10 μM) enhances PAR1-AP-induced PAR1 internalization in HT29 cells, and this effect is blocked by Vorapaxar[5].
Gestodene (10 μM; 30 min) enhances PAR1-AP-induced morphological changes (decreased circularity) in MEG-01 cells, and this effect is blocked by Vorapaxar[5].
Gestodene (GDN) (10-100 nM; 6 h) significantly increases insulin 2 and glucokinase gene expression in isolated rat pancreatic islets[8].
Gestodene (100 nM; 6 h) significantly enhances glucose-stimulated insulin secretion in isolated rat pancreatic islets cultured in 11 mM D-glucose; moreover, in the presence of steroid-metabolizing enzyme inhibitors, the Gestodene-induced increase in insulin 2 and glucokinase gene expression in rat pancreatic islets is suppressed, indicating that the stimulatory effect of Gestodene is exerted through enzyme-generated tetrahydro-reduced metabolites[8].
Gestodene (3 μM; 24 h) enhances PAR1-AP-induced expression of MMP-1, MMP-2, MMP-3, MMP-10, and fibronectin in HaCaT cells as well as COL1A1 expression in NIH-3T3 cells through a PAR1-dependent signaling pathway[4].
Gestodene (10-10-10-6 M; 7 days) abolishes the estradiol-induced cell proliferation effect in T47D-S human breast tumor subclone cells; the proliferation effect induced in T47D-A cells is partially inhibited by antiestrogens (4-Hydroxytamoxifen, ICI 164384) and is not antagonized by antiprogestins (RU 38486 (HY-13683), Org 31710)[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Primary calvarial osteoblasts isolated from neonatal Wistar rats
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Concentration:1, 10, 50, 100, 500 nM
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Incubation Time:15 days
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Result:Showed a significant increase in AP activity at 50 nM and above when compared to vehicle alone.
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Cell Line:Primary calvarial osteoblasts isolated from neonatal Wistar rats
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Concentration:1, 10, 50, 100, 500 nM
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Incubation Time:25 days
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Result:Resulted in a significant increase in cell-associated OC content when compared to cells incubated with vehicle alone.
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Cell Line:Primary calvarial osteoblasts isolated from neonatal Wistar rats
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Concentration:500 nM (Gestodene)
250 µM (Finasteride)
250 µM (Flufenamic acid) -
Incubation Time:15 days
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Result:The presence of finasteride resulted in a complete inhibition of the GDN-induced increase of the AP activity.
The presence of flufenamic acid also inhibited the GDN-induced increase of the AP activity.
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Cell Line:A2058, HaCaT and HDF Cells
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Concentration:3 μM
PAR1-AP (10 μM)
Vorapaxar (30 nM) -
Incubation Time:3 days
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Result:Enhanced PAR1-AP-induced proliferation of A2058, HaCaT, and HDF cells in a PAR1-dependent manner; this enhancing effect can be blocked by Vorapaxar.
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Cell Line:A2058, HaCaT and HDF Cells
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Concentration:3 μM
PAR1-AP (10 μM)
Vorapaxar (30 nM) -
Incubation Time:24 h (A2058 Cells)
14 h (HaCaT Cells)
16 h (HDF Cells) -
Result:Enhanced PAR1-AP-induced migration of A2058, HaCaT, and HDF cells in a PAR1-dependent manner.
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Cell Line:HaCaT and
NIH-3T3 Cells -
Concentration:3 μM
PAR1-AP (10 μM)
Vorapaxar (30 nM) -
Incubation Time:24 h
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Result:Enhanced PAR1-AP-induced expression of MMP-1, MMP-2, MMP-3, MMP-10, fibronectin in HaCaT cells and COL1A1 in NIH-3T3 cells via PAR1-dependent signaling.
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Cell Line:MEG-01 cells
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Concentration:10 μM
PAR1-AP (30 μM)
Vorapaxar (1 μM) -
Incubation Time:10 min
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Result:Enhanced PAR1-AP-induced ERK1/2 phosphorylation in MEG-01 cells through a PAR1-dependent mechanism.
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Cell Line:T47D-A, T47D-S
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Concentration:10-10 M; 10-8 M; 10-6 M
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Incubation Time:7 days
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Result:Stimulated the growth of T47D-A cells but not that of T47D-S cells.
In Vivo
Gestodene (100-600 ng/L; water exposure; renewed daily; 7-day pre-exposure followed by 45 days of continuous exposure) reduces the cumulative egg production per female in adult zebrafish, with no mortality observed, and alters sex steroid levels and mRNA expression of HPG and HPT axis genes in a concentration- and sex-specific manner[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR mice (male, 7 weeks old, 30-32 g)[4]
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Dosage:2 mg/g vaseline, while vorapaxar was applied at a dose of 0.6 mg/vaseline
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Administration:Topical; once daily; 8 consecutive days
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Result:Achieved complete wound closure with 0% residual wound area by Day 8, compared to 22.02% residual wound area in the control group.
Exhibited extensive collagen fiber accumulation, evidenced by prominent blue staining throughout the wound area in Masson's trichrome staining.
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Animal Model:Wild-type (sexually mature, 6-7 months old, both males and females)[6]
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Dosage:100, 600 ng/L
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Administration:waterborne immersion; renewed daily; 45 days
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Result:Reduced female daily egg production, male body length, HSI (both sexes), male 11‑ketotestosterone, and male spermatocyte proportion following gestodene water‑borne exposure.
Altered body weight and female GSI at 600 ng/L gestodene exposure, with zero mortality across tested concentrations.
Modified mRNA levels of cyp19b, npr, mprα, gnih, fshr, pgrmc1, ar, esr1, vtg1, dio1 and dio3‑b in zebrafish brain‑pituitary complex, gonads and liver in concentration‑ and sex‑dependent manners after gestodene treatment.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 60282-87-3
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Appearance Solid
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Masse moléculaire 310.43
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Formule C21H26O2
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Color White to off-white
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SMILES
CC[C@@]1([C@]2(O)C#C)[C@](C=C2)([H])[C@@](CCC3=CC4=O)([H])[C@]([C@@]3([H])CC4)([H])CC1
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Synonyms
SHB 331; WL 70
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : ≥ 100 mg/mL (322.13 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (8.05 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (8.05 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (304 KB)
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SDS (418 KB)
- English - EN (418 KB)
- Français - FR (418 KB)
- Deutsch - DE (418 KB)
- Norwegian - NO (418 KB)
- Español - ES (418 KB)
- Swedish - SV (418 KB)
- Italian - IT (418 KB)
- Korean - KR (418 KB)
- Portuguese - PT (418 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 3.2213 mL | 16.1067 mL | 32.2134 mL | 80.5335 mL |
| 5 mM | 0.6443 mL | 3.2213 mL | 6.4427 mL | 16.1067 mL | |
| 10 mM | 0.3221 mL | 1.6107 mL | 3.2213 mL | 8.0533 mL | |
| 15 mM | 0.2148 mL | 1.0738 mL | 2.1476 mL | 5.3689 mL | |
| 20 mM | 0.1611 mL | 0.8053 mL | 1.6107 mL | 4.0267 mL | |
| 25 mM | 0.1289 mL | 0.6443 mL | 1.2885 mL | 3.2213 mL | |
| 30 mM | 0.1074 mL | 0.5369 mL | 1.0738 mL | 2.6844 mL | |
| 40 mM | 0.0805 mL | 0.4027 mL | 0.8053 mL | 2.0133 mL | |
| 50 mM | 0.0644 mL | 0.3221 mL | 0.6443 mL | 1.6107 mL | |
| 60 mM | 0.0537 mL | 0.2684 mL | 0.5369 mL | 1.3422 mL | |
| 80 mM | 0.0403 mL | 0.2013 mL | 0.4027 mL | 1.0067 mL | |
| 100 mM | 0.0322 mL | 0.1611 mL | 0.3221 mL | 0.8053 mL |
Gestodene Related Classifications
HY-B0110 Related Classifications
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Keywords
- Gestodene
- 60282-87-3
- SHB 331
- WL 70
- SHB331
- SHB-331
- WL70
- WL 70
- WL-70
- Progesterone Receptor
- ERK
- Cytochrome P450
- Protease Activated Receptor (PAR)
- 5 alpha Reductase
- MMP
- Drug Intermediate
- T47D-A cells
- neonatal rat calvarial osteoblasts
- CYP3A
- MCF-7 breast cancer cells
- progesterone receptors
- HT29 cells
- PAR1-selective positive allosteric modulator
- 5α-reductase
- SHBG
- A2058 cells
- Inhibitor
- inhibitor
- inhibit