| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
CYP11A1[1]
Cytochrome P450 11A1 (CYP11A1) |
|---|---|
| ln Vitro |
In vitro enzyme assays show that CYP11A1-IN-1 inhibits CYP11A1 with an IC50 of 201-2000 nM. By blocking CYP11A1 activity, the compound effectively reduces the production of steroid hormones such as glucocorticoids, mineralocorticoids, and sex hormones. It is a selective CYP11A1 inhibitor used for studying steroid receptor-mediated diseases, particularly targeting androgen receptors in conditions like prostate cancer.
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| ln Vivo |
No specific in vivo data for CYP11A1-IN-1. As a CYP11A1 inhibitor, it would be expected to reduce steroid hormone levels in vivo, which could be assessed in animal models of androgen-dependent diseases (e.g., prostate cancer xenografts, benign prostatic hyperplasia). In vivo studies would involve administration to rodents, measuring plasma steroid hormone levels (testosterone, dihydrotestosterone, cortisol, aldosterone) by LC-MS/MS or immunoassay, and assessing effects on tumor growth in xenograft models. The compound is likely orally bioavailable.
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| Enzyme Assay |
Recombinant human CYP11A1 is expressed in E. coli or insect cells, reconstituted with adrenodoxin and adrenodoxin reductase, and purified. The enzyme activity assay measures the conversion of [3H]-cholesterol or [14C]-cholesterol to [3H]-pregnenolone or [14C]-pregnenolone. The reaction is incubated at 37degC for 30-60 minutes in a buffer containing potassium phosphate (pH 7.4), MgCl2, and an NADPH-regenerating system (glucose-6-phosphate, glucose-6-phosphate dehydrogenase, NADP+). The product is extracted with organic solvent, separated by TLC or HPLC, and quantified by scintillation counting. IC50 values are determined from dose-response curves.
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| Cell Assay |
Human adrenocortical cell lines (e.g., H295R) or steroidogenic cell lines are cultured in appropriate media. Cells are treated with CYP11A1-IN-1 (0.1-100 uM) for 24-48 hours. Steroid hormone levels (pregnenolone, progesterone, cortisol, aldosterone, testosterone) in the culture medium are measured by ELISA or LC-MS/MS. CYP11A1 protein expression and activity in cell lysates are assessed by Western blot and enzyme activity assays (as above). Cell viability is assessed by MTT or CellTiter-Glo assays. Cytotoxicity is evaluated by LDH release. Androgen receptor activity can be assessed using a reporter gene assay in AR-responsive cell lines.
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| Animal Protocol |
No published in vivo animal study for this compound. Typical protocols would involve establishing subcutaneous tumor xenografts of androgen-dependent prostate cancer cells (e.g., LNCaP, VCaP) in castrated or intact immunodeficient mice. When tumors reach a certain size, mice are randomized and treated with CYP11A1-IN-1 formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline, or other solubilizers). Dosing is once daily by oral gavage or intraperitoneal injection at doses ranging from 1-100 mg/kg for 2-8 weeks. Endpoints: tumor volume, tumor weight, plasma steroid hormone levels (testosterone, dihydrotestosterone, cortisol, aldosterone) measured by LC-MS/MS, body weight, and survival. Intratumoral steroid levels can also be measured. Target engagement can be assessed by measuring downstream steroid metabolites.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data for CYP11A1-IN-1. As a small molecule inhibitor (molecular weight 466.57, C27H34N2O5), it is expected to have absorption properties favorable for in vivo studies. Physicochemical properties can be estimated from its structure. Solubility: white to light yellow solid, soluble in DMSO. No PK parameters (half-life, Cmax, AUC, clearance, bioavailability, protein binding) are publicly available. Formulation for in vivo studies would need to be developed empirically. Storage: powder at -20degC for 3 years; 4degC for 2 years.
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| Toxicity/Toxicokinetics |
No specific toxicity data for CYP11A1-IN-1. As a CYP11A1 inhibitor, the primary expected on-target toxicity is adrenal insufficiency due to reduced steroid hormone synthesis (glucocorticoid, mineralocorticoid, sex hormone deficiency). This could lead to symptoms such as fatigue, hypotension, electrolyte imbalances, and metabolic disturbances. Off-target effects on other cytochrome P450 enzymes (e.g., CYP17A1, CYP19A1, CYP3A4) are possible, which could affect drug metabolism and other steroidogenic pathways. No genotoxicity or cardiotoxicity data are publicly available.
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| References | |
| Additional Infomation |
CYP11A1-IN-1 (compound 30) is a research tool for studying steroidogenesis, steroid receptor biology, and androgen-dependent diseases (particularly prostate cancer). CYP11A1 is a potential therapeutic target in prostate cancer, as intratumoral androgen synthesis can drive tumor growth even in castration-resistant prostate cancer. Inhibiting CYP11A1 blocks the first step in steroidogenesis, reducing all steroid hormones, including androgens. This compound is not approved for clinical use. Molecular formula: C27H34N2O5, molecular weight: 466.57. It is a selective CYP11A1 enzyme inhibitor. References include its use in research for prostate cancer.
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| Molecular Formula |
C27H34N2O5
|
|---|---|
| Molecular Weight |
466.57
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| Exact Mass |
466.247
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| CAS # |
2744168-51-0
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| PubChem CID |
166850766
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| Appearance |
White to light yellow solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
859
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)OC(=O)N1CC2(C1)CC(C2)COC3=COC(=CC3=O)CN4CCC5=CC=CC=C5C4
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| InChi Key |
FYDVRTQEHDKFTK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H34N2O5/c1-26(2,3)34-25(31)29-17-27(18-29)11-19(12-27)15-33-24-16-32-22(10-23(24)30)14-28-9-8-20-6-4-5-7-21(20)13-28/h4-7,10,16,19H,8-9,11-15,17-18H2,1-3H3
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| Chemical Name |
tert-butyl 6-[[6-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-4-oxopyran-3-yl]oxymethyl]-2-azaspiro[3.3]heptane-2-carboxylate
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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 (214.33 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.36 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1433 mL | 10.7165 mL | 21.4330 mL | |
| 5 mM | 0.4287 mL | 2.1433 mL | 4.2866 mL | |
| 10 mM | 0.2143 mL | 1.0717 mL | 2.1433 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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