| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
Seviteronel R enantiomer targets CYP17A1 (cytochrome P450 17A1), a key enzyme in steroidogenesis that catalyzes both 17alpha-hydroxylase and 17,20-lyase activities. CYP17A1 is essential for the production of androgens and estrogens from cholesterol precursors. By inhibiting CYP17 lyase activity, Seviteronel reduces androgen synthesis without inducing mineralocorticoid excess or cortisol depletion. Seviteronel R enantiomer (VT-464 R enantiomer) is the R enantiomer of Seviteronel, which is a potent CYP17 lyase inhibitor. However, the R enantiomer's activity is unknown. The compound is used in research focused on hormone-dependent cancers.
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| ln Vitro |
In vitro activity of Seviteronel R enantiomer has not been extensively characterized, as the compound is an isomer produced during manufacturing with unknown biological activity. Seviteronel, the parent compound, is a potent CYP17 lyase inhibitor with an h-Lyase IC50 of 69 nM. Seviteronel specifically targets cytochrome P450 17A1, a crucial enzyme in steroidogenesis, and has applications in research focused on hormone-dependent cancers. The R enantiomer is primarily used as a reference standard or for comparative studies to evaluate the stereochemical requirements for CYP17 inhibition. Comprehensive in vitro activity data for the R enantiomer specifically are not available in the public domain.
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| ln Vivo |
In vivo activity of Seviteronel R enantiomer has not been characterized, as the compound is an isomer with unknown biological activity. Seviteronel, the parent compound, is an orally bioavailable, non-steroidal, lyase-selective CYP17 inhibitor with potential anti-androgenic and antineoplastic activities. Seviteronel has been investigated for the treatment of castration-resistant prostate cancer and other hormone-dependent cancers. The R enantiomer is used as a research tool to study the stereochemical aspects of CYP17 inhibition and to evaluate the contribution of each enantiomer to the pharmacological activity of the racemic mixture. Comprehensive in vivo efficacy data for the R enantiomer specifically are not available.
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| Enzyme Assay |
In vitro enzyme assays for Seviteronel R enantiomer involve measuring the inhibition of CYP17 lyase activity. CYP17A1 enzyme (microsomal preparations from cells expressing recombinant CYP17) is incubated with varying concentrations of the test compound and the substrate (e.g., progesterone or pregnenolone). The conversion of the substrate to androgen precursors (e.g., androstenedione or DHEA) is quantified by HPLC or LC-MS/MS. IC50 values are calculated by plotting percent inhibition against compound concentration using non-linear regression analysis. Seviteronel has an h-Lyase IC50 of 69 nM. Selectivity assays compare the compound's activity against other cytochrome P450 enzymes involved in steroidogenesis. Each concentration is typically tested in duplicate or triplicate with appropriate positive controls (known CYP17 inhibitors) and vehicle controls.
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| Cell Assay |
In vitro cellular assays for Seviteronel R enantiomer are performed using hormone-dependent cancer cell lines such as LNCaP or VCaP prostate cancer cells. Cells are treated with varying concentrations of the compound for defined time periods. Androgen production and cell proliferation are measured. Testosterone and dihydrotestosterone (DHT) levels in the culture medium are measured by ELISA or LC-MS/MS. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Apoptosis is measured using annexin V/propidium iodide staining or caspase activity assays. Androgen receptor signaling is assessed by measuring PSA expression or androgen receptor target gene expression by qRT-PCR. Cytotoxicity is assessed in parallel to ensure that observed effects are not due to cell death. IC50 values for inhibition of cell proliferation are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal studies for Seviteronel R enantiomer are not typically conducted, as the compound is an isomer with unknown biological activity. Seviteronel, the parent compound, has been studied in mouse xenograft models of prostate cancer. Immunodeficient mice are implanted subcutaneously with prostate cancer cells and treated with Seviteronel via oral gavage. Tumor growth is measured using calipers. Serum testosterone and other androgen levels are measured to confirm target engagement. Pharmacokinetic studies assess drug concentrations in plasma. The R enantiomer may be used as a reference standard in analytical studies. Comprehensive in vivo efficacy data for the R enantiomer specifically are not available.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Seviteronel R enantiomer have been characterized in preclinical studies. The compound has a molecular formula of C18H17F4N3O3 and a molecular weight of 399.34 g/mol. Its IUPAC name is (R)-1-(6,7-bis(difluoromethoxy)naphthalen-2-yl)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propan-1-ol. The compound is soluble in DMSO (80 mg/mL). Seviteronel is orally bioavailable. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized for Seviteronel. The R enantiomer's pharmacokinetic profile is expected to be similar to that of the racemate.
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| Toxicity/Toxicokinetics |
Seviteronel R enantiomer is intended for laboratory research use only and has not undergone comprehensive toxicology testing. As an isomer of a CYP17 inhibitor, the compound would be expected to have effects on steroidogenesis and hormone-dependent tissues. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has been conducted for Seviteronel. The R enantiomer is not approved for human use and is strictly intended for research purposes.
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| References |
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| Additional Infomation |
Seviteronel R enantiomer (VT-464 R enantiomer) is the R enantiomer of Seviteronel (VT-464, INO-464), a novel, potent, orally bioavailable, non-steroidal, lyase-selective inhibitor of CYP17A1. Seviteronel has an h-Lyase IC50 of 69 nM. However, the R enantiomer's activity is unknown. The compound has a molecular formula of C18H17F4N3O3 and a molecular weight of 399.34 g/mol. Seviteronel R enantiomer is a Seviteronel isomer produced during the manufacturing process. The compound has not entered clinical trials and is available for research purposes only.
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| Molecular Formula |
C18H17F4N3O3
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|---|---|
| Molecular Weight |
399.3395
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| Exact Mass |
399.121
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| CAS # |
1375603-38-5
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| Related CAS # |
Seviteronel;1610537-15-9;Seviteronel racemate;1375603-36-3
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| PubChem CID |
78357817
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| Appearance |
White to off-white solid powder
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| LogP |
4.052
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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-GOSISDBHSA-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-/m1/s1
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| Chemical Name |
(1R)-1-[6,7-bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-(2H-triazol-4-yl)propan-1-ol
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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 : ≥ 100 mg/mL (~250.41 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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