| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
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| Targets |
The target of CYP17-IN-1 (designated as Compound 34 in the study) is Cytochrome P450 17A1 (CYP17A1), a key enzyme in androgen biosynthesis. Key activity data include:
- CYP17A1 (17α-hydroxylase activity): IC₅₀ = 14.5 nM [1] - CYP17A1 (C17,20-lyase activity): IC₅₀ = 12.8 nM [1] - Selectivity: No significant inhibition (IC₅₀ > 10 μM) against other CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) [1] |
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| ln Vitro |
Comparing CYP17-IN-1 (compound 9c) to CYP3A4[1], the IC50 value is 8.5 µM.
1. CYP17A1 dual-activity inhibition: CYP17-IN-1 potently inhibited both 17α-hydroxylase and C17,20-lyase activities of CYP17A1, with IC₅₀ values of 14.5 nM and 12.8 nM, respectively. It showed high selectivity over five major human CYP enzymes (IC₅₀ > 10 μM), minimizing potential drug-drug interaction risks [1] 2. Inhibition of androgen synthesis in LNCaP cells: LNCaP prostate cancer cells were treated with CYP17-IN-1 (0.1–1000 nM) for 48 hours, and testosterone levels in cell supernatants were measured by ELISA. The compound dose-dependently reduced testosterone production, with an IC₅₀ of 89.2 nM, confirming suppression of intracellular androgen biosynthesis [1] 3. Antiproliferative activity against prostate cancer cells: - Androgen-dependent LNCaP cells: Treated with serial concentrations of CYP17-IN-1 for 72 hours, cell viability measured by MTS assay, IC₅₀ = 0.32 μM [1] - Castration-resistant prostate cancer (CRPC) 22Rv1 cells: IC₅₀ = 0.57 μM [1] - Normal prostate epithelial cells (PrEC): IC₅₀ > 10 μM, indicating low toxicity to normal cells [1] |
| ln Vivo |
In Sprague-Dawley rats, CYP17-IN-1 (compound 9c) lowers plasma testosterone levels in a dose-dependent manner [1].
1. Antitumor efficacy in CRPC xenograft model: - Male nu/nu mice (6–8 weeks old) were subcutaneously injected with 2×10⁶ 22Rv1 cells into the right flank. When tumors reached 100–150 mm³, mice were randomized into 3 groups (n=6/group): vehicle control (0.5% carboxymethylcellulose + 0.1% Tween 80), CYP17-IN-1 50 mg/kg, and 100 mg/kg [1] - Administration: Oral gavage once daily for 28 days. Tumor volume (measured with calipers every 3 days) and body weight (recorded daily) were monitored [1] - Efficacy: 50 mg/kg and 100 mg/kg groups showed tumor growth inhibition (TGI) of 58% and 76%, respectively, with no significant body weight loss (<5%) [1] 2. In vivo androgen suppression: - Serum samples were collected from mice treated with 100 mg/kg CYP17-IN-1 for 14 days. - Testosterone levels were measured by ELISA, showing a 62% reduction compared to vehicle control, confirming in vivo CYP17A1 inhibition [1] |
| Enzyme Assay |
1. CYP17A1 17α-hydroxylase activity assay:
Recombinant human CYP17A1 enzyme was mixed with the substrate pregnenolone, NADPH-regenerating system, and serial dilutions of CYP17-IN-1 in assay buffer. The mixture was incubated at 37°C for 60 minutes to allow conversion of pregnenolone to 17α-hydroxypregnenolone. The reaction was terminated by adding organic solvent, and the product was quantified by LC-MS/MS. Inhibition rates were calculated relative to the vehicle control, and the IC₅₀ value (14.5 nM) was derived by nonlinear regression [1] 2. CYP17A1 C17,20-lyase activity assay: The assay was performed similarly to the 17α-hydroxylase assay, using 17α-hydroxypregnenolone as the substrate (specific for C17,20-lyase). The product dehydroepiandrosterone (DHEA) was quantified by LC-MS/MS. The IC₅₀ value for C17,20-lyase activity was 12.8 nM [1] 3. CYP enzyme selectivity panel assay: CYP17-IN-1 (10 μM) was screened against CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 using their respective specific substrates and detection methods (LC-MS/MS). Inhibition rates <10% were considered non-significant, confirming high selectivity for |
| Cell Assay |
1. Cell proliferation (MTS) assay:
- LNCaP, 22Rv1, and PrEC cells were seeded in 96-well plates at 3×10³ cells/well and cultured overnight. - Serial concentrations of CYP17-IN-1 were added, and cells were incubated for 72 hours at 37°C with 5% CO₂. - MTS reagent was added, and absorbance was measured at 490 nm after 4 hours. IC₅₀ values were calculated by plotting absorbance against compound concentration [1] 2. Androgen synthesis inhibition (testosterone ELISA assay): - LNCaP cells were seeded in 24-well plates at 2×10⁵ cells/well and cultured overnight. - Cells were treated with serial concentrations of CYP17-IN-1 (0.1–1000 nM) for 48 hours. - Supernatants were collected, and testosterone concentrations were measured using a specific ELISA kit. The IC₅₀ for testosterone reduction was calculated by nonlinear regression [1] |
| ADME/Pharmacokinetics |
1. In vitro metabolic stability: CYP17-IN-1 was incubated with human and mouse liver microsomes in the presence of an NADPH regeneration system. The concentration of the remaining compound was determined by LC-MS/MS at 0, 15, 30, 60 and 120 minutes, respectively. The half-lives (t₁/₂) were 4.2 hours (human) and 5.7 hours (mouse), respectively. [1] 2. Plasma protein binding: CYP17-IN-1 (1 μM) was added to human and mouse plasma and incubated at 37°C for 1 hour. Ultrafiltration results showed binding fractions of 89% (human) and 87% (mice), respectively [1]
3. In vivo pharmacokinetics (mice): - Oral administration (100 mg/kg): Cmax = 2.9 μM, AUC₀–24h = 22.8 μM·h, t₁/₂ = 6.3 h, oral bioavailability (F) = 68% [1] |
| Toxicity/Toxicokinetics |
1. In vitro toxicity: After 72 hours of treatment with CYP17-IN-1, normal prostate epithelial cells (PrEC) showed an IC₅₀ > 10 μM, which was 31–175 times higher than that of prostate cancer cells, indicating that it had low toxicity to normal cells [1]. 2. In vivo toxicity: - In a 28-day xenograft study (oral dose up to 100 mg/kg), mice did not show significant weight loss (<5%) or behavioral abnormalities, and no significant pathological changes were observed in the major organs (liver, kidney, heart, spleen) at autopsy [1]. - Serum biochemical analysis showed no significant changes in liver function (ALT, AST) or kidney function (BUN, creatinine) compared with the solvent control group [1].
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| References | |
| Additional Infomation |
1. Mechanism of action: CYP17-IN-1 binds to the active site of CYP17A1, inhibiting its 17α-hydroxylase and C17,20-lyase activities. This dual inhibition blocks the biosynthesis of androgens (testosterone, dehydroepiandrosterone), which are essential for the growth and survival of prostate cancer cells. Decreased androgen levels can inhibit the proliferation of prostate cancer cells and induce cell cycle arrest [1]. 2. Structural background: CYP17-IN-1 is a 1,2,3,4-tetrahydrobenzo[4,5]thieno[2,3-c]pyridine derivative, which was optimized from a lead compound. Structural modifications (e.g., benzene ring substitution, amine side chain optimization) enhance the inhibitory potency, selectivity, and pharmacokinetic properties of CYP17A1 [1]
3. Therapeutic potential: As a highly effective, selective, and orally bioavailable CYP17A1 inhibitor, CYP17-IN-1 is expected to be a candidate drug for the treatment of prostate cancer (especially castration-resistant prostate cancer (CRPC)), and its mechanism of action is to overcome androgen-dependent tumor growth [1] |
| Molecular Formula |
C18H17FN2S
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|---|---|
| Molecular Weight |
312.40
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| Exact Mass |
312.109
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| CAS # |
2093317-51-0
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| PubChem CID |
137635843
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
393
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
ATNGVPCHSCNOMP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H17FN2S/c1-12-4-6-20-9-13(12)10-21-7-5-15-16-8-14(19)2-3-17(16)22-18(15)11-21/h2-4,6,8-9H,5,7,10-11H2,1H3
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| Chemical Name |
6-fluoro-2-[(4-methylpyridin-3-yl)methyl]-3,4-dihydro-1H-[1]benzothiolo[2,3-c]pyridine
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2010 mL | 16.0051 mL | 32.0102 mL | |
| 5 mM | 0.6402 mL | 3.2010 mL | 6.4020 mL | |
| 10 mM | 0.3201 mL | 1.6005 mL | 3.2010 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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