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Purity: ≥98%
Seviteronel (VT-464, INO-464) is a novel, potent and orally bioavailable non-steroidal, lyase-selective inhibitor of the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17, IC50=69 nM), with potential anti-androgenic and antineoplastic activities. Upon administration, CYP17 inhibitor VT-464 selectively inhibits the enzymatic activity of the cytochrome P450 C17,20 lyase in both the testes and adrenal glands, thereby inhibiting androgen production.
| 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].
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| 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].
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| References |
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| Additional Infomation |
Seviteronel has been used in trials studying the treatment of CRPC, Prostate Cancer, and Castration-resistant Prostate Cancer.
Seviteronel is an orally available non-steroidal, lyase-selective inhibitor of the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17), with potential anti-androgenic and antineoplastic activities. Upon oral administration, seviteronel selectively inhibits the enzymatic activity of the cytochrome P450 C17,20 lyase in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells. The cytochrome P450 enzyme CYP17A1, localized to the endoplasmic reticulum, exhibits both 17alpha-hydroxylase and 17,20-lyase activities; it plays a key role in the steroidogenic pathway. The lyase-selective activity of seviteronel prevents the increased synthesis of mineralocorticoids that is normally seen with non-selective CYP17 inhibitors, which also inhibit the 17-alpha-hydroxylase activity of CYP17A1. |
| 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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