| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Seviteronel targets cytochrome P450 17A1 (CYP17A1) 17,20-lyase and the androgen receptor (AR). By inhibiting CYP17 lyase, it blocks the synthesis of androgens and estrogens. As an AR antagonist, it directly inhibits androgen receptor signaling. This dual mechanism makes it a potential treatment for castration-resistant prostate cancer.
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| ln Vitro |
Seviteronel (VT-464) is a nonsteroidal small molecule that, without producing excess mineralocorticoid or cortisol depletion, selectively inhibits CYP17, 17, 20-lyase to decrease androgen synthesis. We studied the impact of seviteronel (VT-464) on androgen signaling in C4-2B prostate cancer cells in vitro and on tumor growth in the mCRPC xenograft MDA-PCa-133 in vivo [2].
In vitro, seviteronel inhibits CYP17 lyase activity and antagonizes the androgen receptor. Its activity is measured in enzyme assays and cell-based assays. It inhibits the growth of prostate and breast cancer cells. |
| ln Vivo |
Clinical CRPC bone metastases were used to create MDA-PCa-133 xenografts. The expression of PSA, full-length androgen receptor (AR), and the AR-V7 isoform is observed in subcutaneous MDA-PCa-133 tumors. In tumor-bearing castrated male mice, we examined the effects of Seviteronel (VT-464) and AA on the growth of MDA-PCa-133. The mice were randomly assigned to three groups and given oral vehicle only, VT-464 (100 mg/kg bid), or AA (100 mg/kg bid) for a 25-day period. Tumor volume was decreased by both AA and seviteronel (VT-464) (>2fold relative to vehicle; p<0.05). In this model, these findings suggest that AA CYP17 inhibition is not as effective as selective Seviteronel (VT-464) CYP17 lyase inhibition [2].
In vivo, seviteronel has been studied in preclinical models and clinical trials for the treatment of prostate and breast cancer. It is orally available. It has shown efficacy in reducing tumor growth in animal models. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for seviteronel involves measuring its ability to inhibit CYP17 lyase activity. The enzyme is incubated with its substrate in the presence of varying concentrations of the drug, and the reduction in product formation is measured. The IC50 is determined.
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| Cell Assay |
In vitro cellular assays for seviteronel are performed on prostate and breast cancer cell lines. The inhibition of cell growth is measured using MTT or cell counting assays. Its effects on androgen receptor signaling are measured by quantifying the expression of AR target genes.
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| Animal Protocol |
In vivo animal experiments for seviteronel are conducted in xenograft models of prostate and breast cancer. The drug is administered orally, and its effects on tumor growth, survival, and biomarker expression are assessed.
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| ADME/Pharmacokinetics |
Seviteronel has been evaluated in clinical trials and has characterized pharmacokinetic properties. It is orally bioavailable. Its half-life and metabolism have been studied in humans. It is typically stored as a powder.
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| Toxicity/Toxicokinetics |
Seviteronel has been generally well-tolerated in clinical trials. Common side effects may include fatigue, nausea, and hypertension. It can cause adrenal insufficiency due to its mechanism of action.
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| References |
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| Additional Infomation |
Seviteronel has been used in clinical trials to investigate the treatment of castration-resistant prostate cancer (CRPC), prostate cancer, and castration-resistant prostate cancer. Seviteronel is an oral nonsteroidal anti-inflammatory drug (NSAID) and a selective inhibitor of 17α-hydroxylase/C17,20 lyase (CYP17A1 or CYP17), possessing potential anti-androgenic and antitumor activity. After oral administration, Seviteronel selectively inhibits the enzymatic activity of cytochrome P450 C17,20 lyase in the testes and adrenal glands, thereby inhibiting androgen production. This may reduce androgen-dependent growth signaling and potentially inhibit the proliferation of androgen-dependent tumor cells. The cytochrome P450 enzyme CYP17A1 is located in the endoplasmic reticulum and possesses 17α-hydroxylase and 17,20-lyase activity; it plays a crucial role in the steroidogenic pathway. Sevitronel's lyase-selective activity prevents the increase in mineralocorticoid synthesis that is typically caused by non-selective CYP17 inhibitors, which also inhibit the 17α-hydroxylase activity of CYP17A1.
Seviteronel is an investigational drug for the treatment of prostate and breast cancer. It is also known as VT-464 and INO-464. It is not yet an FDA-approved drug and is in clinical development. |
| Molecular Formula |
C18H17F4N3O3
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|---|---|
| Molecular Weight |
399.3395
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| Exact Mass |
399.12
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| CAS # |
1610537-15-9
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| Related CAS # |
Seviteronel (R enantiomer);1375603-38-5;Seviteronel racemate;1375603-36-3
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| PubChem CID |
78357816
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| Appearance |
White to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
536.3±45.0 °C at 760 mmHg
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| Flash Point |
278.2±28.7 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.562
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| LogP |
3.31
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
517
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)[C@](C1=CC2=CC(=C(C=C2C=C1)OC(F)F)OC(F)F)(C3=NNN=C3)O
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| InChi Key |
ZBRAJOQFSNYJMF-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C18H17F4N3O3/c1-9(2)18(26,15-8-23-25-24-15)12-4-3-10-6-13(27-16(19)20)14(28-17(21)22)7-11(10)5-12/h3-9,16-17,26H,1-2H3,(H,23,24,25)/t18-/m0/s1
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| Chemical Name |
(S)-1-(6,7-bis(difluoromethoxy)naphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-5-yl)propan-1-ol
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| Synonyms |
VT464 VT 464 VT-464 INO-464 INO 464 INO464
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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 : ≥ 50 mg/mL (~125.21 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.26 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 (6.26 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 (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5041 mL | 12.5207 mL | 25.0413 mL | |
| 5 mM | 0.5008 mL | 2.5041 mL | 5.0083 mL | |
| 10 mM | 0.2504 mL | 1.2521 mL | 2.5041 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.
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