| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
HSD11β1 (hydroxysteroid (11-beta) dehydrogenase 1). [1]
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| ln Vitro |
The HCCLM3 and MDA-MB-231 cells' expression of Snail and Slug was substantially decreased by epinephrine. The highly metastatic human cancer cells (HCCLM3, MDA-MB-231, and MDA-MB-435 cells) are inhibited in their ability to move and invade by epinephrine [1]. Epinephrine functions as a competitive inhibitor of HSD11β1, facilitating the interconversion of the stress hormone cortisol and the inactive metabolite cortisone. Cortisol levels are lowered by epinephrine [1].
Adrenosterone did not affect cell viability of HCCLM3, MDA-MB-231, and MDA-MB-435 cells at the concentrations tested. [1] Adrenosterone inhibited cell motility and invasion of HCCLM3, MDA-MB-231, and MDA-MB-435 cells in a dose-dependent manner as assessed by Boyden chamber assay using 1% FBS as chemoattractant. [1] Western blot analysis showed that adrenosterone-treated HCCLM3 and MDA-MB-231 cells had markedly decreased expression of Snail and Slug compared with vehicle-treated cells. [1] Adrenosterone treatment restored E-cadherin expression in HCCLM3 and MDA-MB-231 cells at both the mRNA and protein levels compared with vehicle-treated cells. [1] Adrenosterone-treated cells did not show decreased expression of mesenchymal markers such as N-cadherin and vimentin compared with vehicle-treated cells. [1] FACS analysis demonstrated that the percentage of E-cadherin-positive cells (E-cad+ cells) in adrenosterone-treated HCCLM3 cells was approximately 30%. Immunofluorescence analysis revealed that E-cad+ cells showed cell-cell adhesion, whereas E-cadherin-negative cells maintained loss of cell-cell contact. [1] mRNA expression of other EMT-related epithelial markers (CDH1, OCLN, CLDN3, CLDN6, CLDN7, KRT14, KRT19) in adrenosterone-treated HCCLM3 cells was increased compared with vehicle-treated cells. [1] |
| ln Vivo |
In the Twist1a-ERT2/xmrk double transgenic zebrafish model, adrenosterone treatment (administered at 5 μmol/L in E3 medium containing doxycycline and 4-OHT for 5 days) significantly reduced the frequencies of abdominal and distant dissemination of mCherry-labeled hepatic cells. The frequencies of abdominal and distant dissemination in the adrenosterone-treated group decreased to 2.94% ± 4.16% and 0%, respectively, compared with vehicle-treated group (53.33% ± 2.11% and 46.41% ± 2.78%). Conversely, the frequency of fish showing no cell dissemination increased to 94.92% ± 1.15% in the adrenosterone-treated group versus 27.77% ± 2.70% in vehicle-treated group. Adrenosterone did not affect primary tumor growth (liver size, PCNA-positive cells, cleaved caspase 3-positive cells, or survival) in this model. [1]
In a zebrafish xenotransplantation model using RFP-labeled HCCLM3 cells injected into the duct of Cuvier of Tg(kdrl:eGFP) zebrafish at 2 dpf, adrenosterone treatment significantly suppressed metastatic dissemination. The frequencies of fish showing head, trunk, or end-tail dissemination in the adrenosterone-treated group decreased to 55.3% ± 7.5%, 28.5% ± 5.0%, and 43.5% ± 19.1%, respectively, compared with vehicle-treated group (95.8% ± 5.8%, 47.1% ± 7.7%, and 82.6% ± 12.7%). The frequency of fish showing no dissemination increased to 45.4% ± 0.5% in the adrenosterone-treated group versus 2.0% ± 2.9% in vehicle-treated group. Similar effects were observed in xenotransplantation experiments using RFP-labeled MDA-MB-231 cells. [1] |
| Cell Assay |
Cell viability assay: Cells (HCCLM3, MDA-MB-231, MDA-MB-435) were treated with vehicle or adrenosterone (concentrations not specified), and cell viability was assessed. Adrenosterone did not affect cell viability of these cells. [1]
Boyden chamber assay: Either 3×10^5 MDA-MB-231, 5×10^5 HCCLM3, or 1×10^6 MDA-MB-435 cells were applied to each top well. Cells were treated with vehicle or adrenosterone. FBS (1% v/v) was used as the chemoattractant. Cell motility and invasion were measured. Adrenosterone inhibited cell motility and invasion in a dose-dependent manner. [1] Western blot analysis: Cells were treated with vehicle or adrenosterone, lysed, and subjected to Western blot using antibodies against Snail, Slug, E-cadherin, N-cadherin, vimentin, HSD11β1, GAPDH, and others. Adrenosterone decreased Snail and Slug expression, restored E-cadherin expression, but did not alter N-cadherin or vimentin levels. [1] RT-qPCR: Total RNA was extracted from adrenosterone- or vehicle-treated cells, cDNA synthesized, and qPCR performed using SYBR-Green Master PCR Mix with primers for CDH1, OCLN, CLDN3, CLDN6, CLDN7, KRT14, KRT19, and GAPDH as endogenous control. Adrenosterone increased mRNA expression of these epithelial markers. [1] FACS analysis: Adrenosterone-treated HCCLM3 cells were stained for E-cadherin and analyzed by flow cytometry. Approximately 30% of cells were E-cadherin-positive. [1] Immunofluorescence microscopy: Cells were fixed, stained with anti-E-cadherin antibody followed by Alexa Fluor 488-conjugated secondary antibody, and nuclei visualized with DAPI. E-cadherin-positive cells showed cell-cell adhesion, whereas negative cells did not. [1] |
| Animal Protocol |
In vivo drug screening in Twist1a-ERT2/xmrk double transgenic zebrafish: Larvae at 8 days postfertilization (dpf) were treated with 30 μg/mL doxycycline in E3 medium for 3 days to induce xmrk expression. Approximately 20 larvae were aliquoted into each well of a 6-well plate with 8 mL E3 medium containing doxycycline. Adrenosterone was added to each well at a final concentration of 5 μmol/L. Twelve hours after drug addition, 4-OHT was added at a final concentration of 0.1 μmol/L to induce Twist1a-ERT2 activity. Five days after drug addition, larvae were examined under a fluorescence microscope and dissemination patterns of mCherry-labeled cells from the liver were quantified. [1]
Large-scale validation: Similar protocol as above with adrenosterone at 5 μmol/L; frequencies of dissemination patterns were determined from two independent experiments. [1] Zebrafish xenotransplantation model: Zebrafish embryos (Tg(kdrl:eGFP) line) at 2 dpf were maintained in E3 medium containing 200 μmol/L 1-phenyl-2-thiourea. Approximately 100-400 RFP-labeled HCCLM3 or MDA-MB-231 cells were injected into the duct of Cuvier. After injection, fish were maintained in the presence of vehicle or adrenosterone (concentration not specified). Twenty-four hours post-injection, the frequencies of fish showing metastatic dissemination (head, trunk, end-tail) were measured under fluorescence microscopy. [1] |
| ADME/Pharmacokinetics |
Adrenosterone is metabolically “downstream” from cortisol and cortisone as it lacks the C20‑C21 corticosteroid side‑chain.
- Administration of adrenosterone leads to increased urinary excretion of the 11‑oxy‑C19 endogenous glucocorticoid metabolites (11β‑OHEt, 11‑oxoEt, 11β‑OHA) and their concomitant depletion in 13C as measured by GC‑C‑IRMS. - The δ13C value of the adrenosterone substrate in the administered capsule was −30.4‰ ±0.5‰ (n=7). |
| Toxicity/Toxicokinetics |
Adrenosterone did not show lethal effects on Twist1a-ERT2/xmrk double transgenic zebrafish at the tested concentration (5 μmol/L). One drug (not adrenosterone) in the screen had a lethal effect on the fish. [1]
Adrenosterone did not affect primary tumor growth in the zebrafish model: treated fish showed enlarged livers similar to vehicle-treated fish; liver size, frequencies of PCNA-positive cells, and cleaved caspase 3-positive cells in the livers were the same as vehicle-treated fish; survival analysis showed adrenosterone-treated fish survived as long as vehicle-treated fish. [1] Adrenosterone did not affect cell viability of HCCLM3, MDA-MB-231, and MDA-MB-435 cells. [1] |
| References |
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| Additional Infomation |
Adrenosterone is a 3-oxoΔ⁴ steroid belonging to the androstane-4-ene family, with three oxo substituents at positions 3, 11, and 17. It is an androgen found in human urine and marine organisms, and is an inhibitor of EC 1.1.1.146 (11β-hydroxysteroid dehydrogenase). It is a 3-oxoΔ⁴ steroid, a 17-oxo steroid, an androstane compound, and an 11-oxo steroid. It is derived from the hydrogenation of androstane.
Adrenosterone is a competitive inhibitor of HSD11β1, an enzyme that catalyzes the interconversion of the steroid pair of the inactive metabolite cortisone and the stress hormone cortisol. Adrenosterone decreases the amount of cortisol. It was originally isolated from the adrenal cortex of fish as a steroid hormone with a weak androgenic effect and is currently used as a daily supplement for bodybuilders. This study provides the first evidence that elevated HSD11β1 expression is observed only in highly metastatic human cell lines (MDA-MB-231, MDA-MB-435, HCCLM3, MIA-PaCa2, PC3, SW620) but not in poorly metastatic cell lines (MCF7). Pharmacologic inhibition of HSD11β1 by adrenosterone suppressed spontaneous cell dissemination from a primary tumor site and metastatic dissemination of human cancer cells in zebrafish models. Genetic inhibition of HSD11β1 by shRNA showed similar effects. Adrenosterone is suggested to interfere with acquired mesenchymal traits of cancer cells through downregulation of Snail and Slug, leading to recovery of E-cadherin and other epithelial markers, without reversing mesenchymal markers such as vimentin. [1] |
| Molecular Formula |
C19H24O3
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|---|---|
| Molecular Weight |
300.3921
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| Exact Mass |
300.172
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| CAS # |
382-45-6
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| PubChem CID |
223997
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
476.1±45.0 °C at 760 mmHg
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| Melting Point |
219-222 °C(lit.)
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| Flash Point |
206.0±23.9 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.561
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| LogP |
1.19
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
22
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| Complexity |
616
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2C(=O)C[C@]4([C@H]3CCC4=O)C
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| InChi Key |
RZRPTBIGEANTGU-IRIMSJTPSA-N
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| InChi Code |
InChI=1S/C19H24O3/c1-18-8-7-12(20)9-11(18)3-4-13-14-5-6-16(22)19(14,2)10-15(21)17(13)18/h9,13-14,17H,3-8,10H2,1-2H3/t13-,14-,17+,18-,19-/m0/s1
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| Chemical Name |
(8S,9S,10R,13S,14S)-10,13-dimethyl-1,2,6,7,8,9,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,11,17-trione
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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 |
| 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) |
DMSO : ~25 mg/mL (~83.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.92 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 20.8 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: ≥ 2.08 mg/mL (6.92 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 20.8 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: ≥ 2.08 mg/mL (6.92 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 | 3.3290 mL | 16.6450 mL | 33.2901 mL | |
| 5 mM | 0.6658 mL | 3.3290 mL | 6.6580 mL | |
| 10 mM | 0.3329 mL | 1.6645 mL | 3.3290 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 |
| NCT05263557 | Recruiting | Dietary Supplement: 11-ketoandrostenedione (11KA4) |
Polycystic Ovary Syndrome Insulin Resistance |
Royal College of Surgeons, Ireland | August 19, 2022 | Not Applicable |
| NCT05246865 | Recruiting | Drug: oral androgen challenge with dehydroepiandrosterone (DHEA) |
Polycystic Ovary Syndrome | University of Birmingham | October 10, 2021 | Not Applicable |
| NCT03578497 | Completed | Drug: IL-1 receptor antagonist Anakinra | Polycystic Ovary Syndrome | University Hospital, Basel, Switzerland | August 31, 2018 | Phase 2 |
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