| Size | Price | Stock | Qty |
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| 10mg |
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D4-abiraterone is an androgen receptor antagonist with an IC50 of 5.3 nM and an active metabolite of abiraterone Δ4-Abiraterone (D4A), an inhibitor of CYP17A1, an androgen receptor. An authorized anticancer drug, biratterone (previously CB-7598; Zytiga), functions as a selective and irreversible CYP17 inhibitor.
| ln Vitro |
D4-abiraterone (D4A ) (10 mM) almost totally prevents the conversion of D4-androstenedione (AD) into 5α-androstanedione and other 5α-reduced androgens. Abiraterone (Abi) (IC50=418 and >500 nM, respectively) has a lower affinity for the mutant and wild type androgen receptors (IC50=5.3 nM and 7.9 nM, respectively) than does D4-abiraterone (expressed in LNCaP and IC50=5.3 nM). When it comes to suppressing PSA, TMPRSS2, and FKBP5 expression in LNCAP, LAPC4, and C4-2 cell lines, D4-abiraterone performs a notably better job than Albi. The expression of AR target genes is also dose-dependently inhibited by D4-abiraterone[1].
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| ln Vivo |
D4-abiraterone (D4A) is ten times more effective than abiraterone (Abi) at preventing the conversion of dehydroepiandrosterone (DHEA) to D4-androstenedione (AD) by 3β-hydroxysteroid dehydrogenase (3βHSD) in LNCaP and VCaP xenografts. For the purpose of preventing AD accumulation at 48 hours in both LNCaP and VCaP xenografts, 0.1 μM D4-abiraterone is equal to 1 μM Abi. When comparing the D4-abiraterone group to the Abi acetate group, there is a significant delay in progression (P=0.011). When compared to Abi acetate, treatment with D4-abiraterone improves progression-free survival[1].
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| Enzyme Assay |
Enzyme assays are used to determine whether D4-abiraterone (D4A) is an inhibitor of 3βHSD. In summary, 0.5 mL of potassium phosphate buffer (pH 7.4), D4-abiraterone (5 to 20 μM), or ethanol vehicle are prepared along with recombinant human 3βHSD1 or 3βHSD2 (in yeast microsomes, 45 or 2.5 μg protein per incubation, respectively). NAD+ (1 mM) is added after a pre-incubation at 37°C for 1 to 3 min, and the incubation is carried out at 37°C for 20 min. The addition of 1 mL of ethyl acetate:isooctane (1:1) stops the reaction, after which the steroids are extracted into the organic phase and dried. In-line scintillation counting is used to quantify the steroids in the dried extracts, and HPLC is used to resolve the steroids[1].
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| Cell Assay |
The indicated concentrations of D4-abiraterone (D4A) are applied to the cells for 30 minutes after they have been cultured for 48 hours in serum-free medium. The cells are lysed using RIPA buffer after being washed twice with 0.9% NaCl solution and four times with 1×PBS. A multilabel counter is used to detect the protein concentration, which is then used to normalize the intracellular radioactivity measured using a liquid scintillation counter|1].
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| Animal Protocol |
In this study, male NSG mice aged 6 to 8 weeks are employed. Mice with castration-resistant prostate cancer (CRPC) are surgically orchiectomized and given a 5 mg sustained-release dehydroepiandrosterone (DHEA) pellet to be administered over a 90-day period, simulating human adrenal physiology. Two days later, matrigel is subcutaneously injected with 107 VCaP or C4-2 cells. Mice are randomly assigned, without following strict randomization, to treatment groups consisting of either vehicle (n = 9 or 10 mice for VCaP and C4-2, respectively) or D4-abiraterone (n = 10 mice for both cell lines) once tumors reach 300mm3. For up to 15 days, 5 mL per kg intraperitoneal injection of D4-abiraterone (0.5 mmol per kg per day in 0.1 mL 5% benzyl alcohol and 95% safflower oil solution) is given daily. Every day, intraperitoneal injections of 0.1 mL of a 5% benzyl alcohol and 95% safflower oil solution are given to the control groups. Every day, the volume of the tumor is measured, and the time it takes for the tumor to grow by 20% is calculated. When the tumor size doubles over the baseline or on day 15 of treatment, mice are killed[1].
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| References |
| Molecular Formula |
C24H29NO
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|---|---|
| Molecular Weight |
347.49316
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| Exact Mass |
347.22
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| Elemental Analysis |
C, 82.95; H, 8.41; N, 4.03; O, 4.60
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| CAS # |
154229-21-7
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| Related CAS # |
154229-21-7
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| Appearance |
Solid powder
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| SMILES |
C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4C5=CN=CC=C5)C
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| InChi Key |
GYJZZAJJENTSTP-NHFPKVKZSA-N
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| InChi Code |
InChI=1S/C24H29NO/c1-23-11-9-18(26)14-17(23)5-6-19-21-8-7-20(16-4-3-13-25-15-16)24(21,2)12-10-22(19)23/h3-4,7,13-15,19,21-22H,5-6,8-12H2,1-2H3/t19-,21-,22-,23-,24+/m0/s1
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| Chemical Name |
(8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one
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| Synonyms |
CB 7627; D4A; Δ4-Abiraterone
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 (~143.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.19 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 (7.19 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 | 2.8778 mL | 14.3889 mL | 28.7778 mL | |
| 5 mM | 0.5756 mL | 2.8778 mL | 5.7556 mL | |
| 10 mM | 0.2878 mL | 1.4389 mL | 2.8778 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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