| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
ASP9521 targets aldo-keto reductase 1C3 (AKR1C3 / 17βHSD5), an enzyme involved in the conversion of androstenedione (AD) into testosterone (T). It inhibits recombinant human AKR1C3 with an IC50 of 11 nM and cynomolgus monkey AKR1C3 with an IC50 of 49 nM. ASP9521 displays >100-fold selectivity for AKR1C3 over the isoform AKR1C2, and does not inhibit AKR1C1 or AKR1C6. By inhibiting AKR1C3, it reduces intratumoral testosterone production.
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| ln Vitro |
Given the potential for total androgen blocking when AKR1C3 inhibitors and gonadotropin-releasing hormone analogues are used together, AKR1C3 is a prospective therapeutic target in castration-resistant prostate cancer. In a concentration-dependent manner, ASP-9521 prevents recombinant human or cynomolgus monkey AKR1C3 from converting androstenedione (AD) to androstenedione and testosterone (T) (IC50, human: 11 nM; IC50, monkey: 49 nM). ASP-9521 has a selectivity of over 100 times for AKR1C3 relative to AKR1C2 isoform. ASP-9521 suppresses AD-dependent PSA synthesis and cell division in LNCaP-AKR1C3 cells [1].
In vitro, ASP9521 inhibits both androstenedione (10 nM)-induced PSA production and cell proliferation in LNCaP-AKR1C3 cells with IC50 values of 11 nM and 6.6 nM, respectively. It inhibits the conversion of androstenedione into testosterone by recombinant human or cynomolgus monkey AKR1C3 in a concentration-dependent manner. The compound's high selectivity and potent activity against AKR1C3 make it a valuable tool for studying the role of this enzyme in prostate cancer and other diseases. |
| ln Vivo |
A single oral dosage of ASP-9521 (3 mg/kg) reduced AD-induced intratumoral T production in CWR22R xenografts, and this suppression lasted for a full day. Following oral dosing, ASP-9521 remains highly concentrated in the intratumoral region but is quickly removed from plasma. ASP-9521 has an oral dosage of 1 mg/kg, and its bioavailability in rats, dogs, and monkeys is 35%, 78%, and 58%, respectively [1].
In vivo, ASP9521 (3 and 10 mg/kg) inhibits androstenedione-induced intratumor testosterone production in a CWR22R prostate cancer mouse xenograft model. The compound has demonstrated anti-tumour activity in preclinical models. Its oral bioavailability makes it suitable for in vivo efficacy studies and supports its development as a therapeutic agent for castration-resistant prostate cancer. |
| Enzyme Assay |
The in vitro enzymatic activity of ASP9521 is assessed using cell-free enzyme assays with recombinant human or cynomolgus monkey AKR1C3. The enzyme is incubated with its substrate, androstenedione, and cofactor NADPH in the presence of varying concentrations of the inhibitor. The conversion of androstenedione to testosterone is measured using chromatographic or radiometric methods. The IC50 values (11 nM for human AKR1C3 and 49 nM for monkey AKR1C3) are determined from dose-response curves. Selectivity profiling against other AKR1C isoforms is performed using similar enzyme assays.
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| Cell Assay |
To evaluate the cellular effects of ASP9521, LNCaP-AKR1C3 cells are treated with the compound. Androstenedione-induced PSA production is measured as a marker of androgen receptor activity. Cell proliferation is assessed using standard assays such as MTT or CellTiter-Glo. The IC50 values for inhibition of PSA production (11 nM) and cell proliferation (6.6 nM) are determined from dose-response curves.
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| Animal Protocol |
In vivo studies with ASP9521 typically involve administration to tumor-bearing mice in xenograft models, such as the CWR22R prostate cancer model. The compound is administered via oral routes at doses such as 3 and 10 mg/kg. Intratumoral testosterone production is measured following androstenedione challenge. Tumor growth inhibition and other efficacy endpoints are assessed. Pharmacokinetic parameters, such as oral bioavailability, are also characterized.
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| ADME/Pharmacokinetics |
ASP9521 has a molecular formula of C19H26N2O3 and a molecular weight of 330.42 g/mol. Its CAS number is 1126084-37-4. The compound has a purity of ≥98%. It is soluble in DMSO (10 mM). It is also known as ASP-9521, AKR1C3 inhibitor, and 17βHSD5 inhibitor.
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| Toxicity/Toxicokinetics |
Specific toxicology data for ASP9521 are not extensively detailed in the available literature. However, its use in preclinical models at effective doses suggests a degree of tolerability. As with all research compounds, standard safety precautions should be taken when handling ASP9521. It is intended for research use only and is not for human consumption.
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| 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
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| Additional Infomation |
ASP9521, a selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17bHSD5, AKR1C3, aldosterone reductase 1C3), possesses potential antitumor activity. Upon administration, ASP9521 selectively binds to and inhibits the activity of 17bHSD5. This prevents the conversion of adrenal androgens dehydroepiandrosterone (DHEA) and androstenedione to 5-androstenedione and testosterone. By blocking testosterone production, ASP9521 may inhibit the growth of testosterone-dependent cancers, such as castration-resistant prostate cancer (CRPC). 17bHSD5 is expressed in both normal prostate tissue and prostate cancer (PC) and plays a crucial role in the sustained production of androgens after castration. Its expression is associated with increased malignancy in prostate cancer.
ASP9521 is a potent and selective AKR1C3 inhibitor that has been investigated for the treatment of castration-resistant prostate cancer. By inhibiting AKR1C3, it reduces intratumoral testosterone production, which is a key driver of prostate cancer progression. The compound has demonstrated anti-tumour activity in preclinical models. It is a research tool for studying the role of AKR1C3 in cancer and other diseases and is not a clinically approved drug. |
| Molecular Formula |
C19H26N2O3
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| Molecular Weight |
330.42
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| Exact Mass |
330.194
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| CAS # |
1126084-37-4
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| Related CAS # |
1126084-37-4
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| PubChem CID |
25210792
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
543.9±30.0 °C at 760 mmHg
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| Flash Point |
282.7±24.6 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.599
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| LogP |
0.62
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
446
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])C([H])([H])C([H])([H])N(C(C2=C([H])C3C([H])=C(C([H])=C([H])C=3N2[H])OC([H])([H])[H])=O)C([H])([H])C1([H])[H]
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| InChi Key |
OXSCPDKUZWPWFR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H26N2O3/c1-19(2,23)12-13-6-8-21(9-7-13)18(22)17-11-14-10-15(24-3)4-5-16(14)20-17/h4-5,10-11,13,20,23H,6-9,12H2,1-3H3
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| Chemical Name |
(4-(2-hydroxy-2-methylpropyl)piperidin-1-yl)(5-methoxy-1H-indol-2-yl)methanone.
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| Synonyms |
ASP9521 ASP-9521 ASP 9521. AKR1C3 inhibitor 17HSD5 inhibitor
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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 (~302.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.57 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 (7.57 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*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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