ASP-9521
(Synonyms: 1-[1-[(5-甲氧基-1H-吲哚-2-基)羰基]哌啶-4-基]-2-甲基丙-2-醇) 目录号 : GC32936
An inhibitor of 17β-HSD5/AKR1C3
Cas No.:1126084-37-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | LNCaP-AKR1C3 cells stably expressing human AKR1C3 are seeded in 96-well plates at 10000 cells/100 μL/well in RPMI-1640 medium supplemented with heat-inactivated charcoal-dextran-stripped FBS (1 % for the PSA expression assay and T measurement and 5 % for the cell proliferation assay). After 24 h incubation, AD is added to each well with or without ASP-9521 (0.3-100 nM). The cell culture media are collected 24 h after administration of AD to measure T concentration and 6 days after administration of AD to measure cell proliferation using Cell-Titer Glo assay[1]. |
Animal experiment: | Mice carrying HEK293 or HEK293-AKR1C3 tumours with similar sizes are selected and randomly divided into 5 groups (N=3 for each group). All groups are treated with ASP-9521 (single oral administration; 3 mg/kg). Plasma (from the central vein) and tumour tissues are collected at 0.25, 0.5, 1, 2 and 4 h after administration of ASP-9521, and ASP-9521 concentrations are determined using the HPLCMS/MS method[1]. |
References: [1]. Kikuchi A, et al. In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3).Invest New Drugs. 2014 Oct;32(5):860-70. | |
ASP9521 is an inhibitor of 17β-hydroxysteroid dehydrogenase type 5/aldo-keto reductase 1C3 (17β-HSD5/AKR1C3; IC50 = 120 nM).1 It is selective for 17β-HSD5/AKR1C3 over AKR1C2 (IC50 = 20 μM). ASP9521 inhibits conversion of androstenedione into testosterone by 17β-HSD5/AKR1C3 (IC50s = 11 and 49 nM for human and cynomolgus monkey enzymes, respectively). It inhibits androstenedione-dependent production of prostate specific androgen (PSA) in and proliferation of LNCaP cells expressing 17β-HSD5/AKR1C3. ASP9521 (3 and 10 mg/kg) inhibits androstenedione-induced intratumor testosterone production in a CWR22R prostate cancer mouse xenograft model.
1.Kikuchi, A., Furutani, T., Azami, H., et al.In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3).Invest New Drugs32(5)860-870(2014)
| Cas No. | 1126084-37-4 | SDF | |
| 别名 | 1-[1-[(5-甲氧基-1H-吲哚-2-基)羰基]哌啶-4-基]-2-甲基丙-2-醇 | ||
| Canonical SMILES | O=C(N1CCC(CC(C)(O)C)CC1)C(N2)=CC3=C2C=CC(OC)=C3 | ||
| 分子式 | C19H26N2O3 | 分子量 | 330.42 |
| 溶解度 | DMSO : ≥ 300 mg/mL (907.94 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0265 mL | 15.1323 mL | 30.2645 mL |
| 5 mM | 0.6053 mL | 3.0265 mL | 6.0529 mL |
| 10 mM | 0.3026 mL | 1.5132 mL | 3.0265 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Inhibition of castration-resistant prostate cancer growth by genistein through suppression of AKR1C3
Food Nutr Res 2023 Jan 31;67.PMID:36794010DOI:PMC9899042
Background: Prostate cancer is the second leading cause of cancer-related death among males in America. The patients' survival time is significantly reduced after prostate cancer develops into castration-resistant prostate cancer (CRPC). It has been reported that AKR1C3 is involved in this progression, and that its abnormal expression is directly correlated with the degree of CRPC malignancy. Genistein is one of the active components of soy isoflavones, and many studies have suggested that it has a better inhibitory effect on CRPC. Objective: This study aimed to investigate the antitumor effect of genistein on CRPC and the potential mechanism of action. Design: A xenograft tumor mouse model established with 22RV1 cells was divided into the experimental group and the control group, and the former was given 100 mg/kg.bw/day of genistein, with 22RV1, VCaP, and RWPE-1 cells cultured in a hormone-free serum environment and treated with different concentrations of genistein (0, 12.5, 25, 50, and 100 μmol/L) for 48 h. Molecular docking was used to elucidate the molecular interactions between genistein and AKR1C3. Results: Genistein inhibits CRPC cell proliferation and in vivo tumorigenesis. The western blot analysis confirmed that the genistein significantly inhibited prostate-specific antigen production in a dose-dependent manner. In further results, AKR1C3 expression was decreased in both the xenograft tumor tissues and the CRPC cell lines following genistein gavage feeding compared to the control group, with the reduction becoming more obvious as the concentration of genistein was increased. When the genistein was combined with AKR1C3 small interfering ribonucleic acid and an AKR1C3 inhibitor (ASP-9521), the inhibitory effect on the AKR1C3 was more pronounced. In addition, the molecular docking results suggested that the genistein had a strong affinity with the AKR1C3, and that it could be a promising AKR1C3 inhibitor. Conclusion: Genistein inhibits the progression of CRPC via the suppression of AKR1C3.