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MedKoo Cat#: 205818 | Name: ASP9521
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

ASP9521 is a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3). ASP9521 has demonstrated anti-tumour activity in in vitro and in vivo preclinical models. ASP9521 inhibited conversion of androstenedione (AD) into testosterone (T) by recombinant human or cynomolgus monkey AKR1C3 in a concentration-dependent manner (IC50,human: 11 nmol/L; IC50,monkey: 49 nmol/L). ASP9521 showed >100-fold selectivity for AKR1C3 over the isoform AKR1C2. In LNCaP-AKR1C3 cells, ASP9521 suppressed AD-dependent PSA production and cell proliferation. In patients with mCRPC, ASP9521 demonstrated dose-proportional increase in exposure over the doses evaluated, with an acceptable safety and tolerability profile. However, the novel androgen biosynthesis inhibitor showed no relevant evidence of clinical activity.

Chemical Structure

ASP9521
ASP9521
CAS#1126084-37-4

Theoretical Analysis

MedKoo Cat#: 205818

Name: ASP9521

CAS#: 1126084-37-4

Chemical Formula: C19H26N2O3

Exact Mass: 330.1943

Molecular Weight: 330.42

Elemental Analysis: C, 69.06; H, 7.93; N, 8.48; O, 14.53

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 180.00 Ready to ship
50mg USD 305.00 Ready to ship
100mg USD 550.00 Ready to ship
200mg USD 950.00 Ready to ship
500mg USD 2,050.00 Ready to ship
1g USD 3,750.00 2 Weeks
2g USD 6,250.00 2 Weeks
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Related CAS #
No Data
Synonym
ASP9521; ASP-9521; ASP 9521. AKR1C3 inhibitor ; 17HSD5 inhibitor
IUPAC/Chemical Name
(4-(2-hydroxy-2-methylpropyl)piperidin-1-yl)(5-methoxy-1H-indol-2-yl)methanone.
InChi Key
OXSCPDKUZWPWFR-UHFFFAOYSA-N
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
SMILES Code
O=C(N1CCC(CC(C)(O)C)CC1)C(N2)=CC3=C2C=CC(OC)=C3
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
ASP-9521 is an AKR1C3 inhibitor with an IC50 of 11 nM for human AKR1C3.
In vitro activity:
The AKR1C3 inhibition potency of the lead compounds were slightly less to those determined for two AKR1C3 inhibitors developed by industry GTx-560 and ASP9521, Table 2. Compound 1, GTx-560 and ASP9521 all inhibited the conversion of Δ4-AD to testosterone in LNCaP-AKR1C3 cells consistent with the competitive inhibition observed with these agents. However, there is a difference in potency of the compounds based on the in vitro enzyme assays and the assays performd in LNCaP-AKR1C3 cells, which may be related to cell permeability issues. All the inhibitors are carboxylic acids and would likely require transport by OATPs for cell entry. Reference: J Steroid Biochem Mol Biol. 2019 Sep; 192: 105283. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625945/
In vivo activity:
To investigate ASP9521 accumulation, the concentration of ASP9521 in plasma and tumour tissue was measured over time in nude mice bearing HEK293 tumours with or without AKR1C3 expression. After single oral administration of ASP9521, plasma concentrations of ASP9521 reached maximum values within 0.25 h (mean: 767.3 ng/mL and 648.2 ng/mL for HEK293 and HEK293-AKR1C3 cells, respectively), but decreased rapidly thereafter (Fig. 10). Similarly, the intratumoural concentration of ASP9521 in HEK293 tumours lacking AKR1C3 expression rapidly decreased from 845.8 ng/g after 0.25 h to undetectable levels after 4 h. In contrast, in HEK293 tumours expressing AKR1C3, the maximum intratumoural ASP9521 concentration was considerably higher (mean: 1,905.0 ng/g after 0.25 h), and elevated ASP9521 levels were maintained for at least 4 h. These results suggest that accumulation of ASP9521 in tumour tissue may depend on AKR1C3 expression. Reference: Invest New Drugs. 2014 Oct;32(5):860-70. https://pubmed.ncbi.nlm.nih.gov/24981575/
Solvent mg/mL mM
Solubility
DMSO 52.3 158.16
DMF 10.0 30.26
DMF:PBS (pH 7.2) (1:1) 0.5 1.51
Ethanol 36.4 110.01
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 330.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Wangtrakuldee P, Adeniji AO, Zang T, Duan L, Khatri B, Twenter BM, Estrada MA, Higgins TF, Winkler JD, Penning TM. A 3-(4-nitronaphthen-1-yl) amino-benzoate analog as a bifunctional AKR1C3 inhibitor and AR antagonist: Head to head comparison with other advanced AKR1C3 targeted therapeutics. J Steroid Biochem Mol Biol. 2019 Sep;192:105283. doi: 10.1016/j.jsbmb.2019.01.001. Epub 2019 Jan 11. PMID: 30641225; PMCID: PMC6625945. 2. Kikuchi A, Furutani T, Azami H, Watanabe K, Niimi T, Kamiyama Y, Kuromitsu S, Baskin-Bey E, Heeringa M, Ouatas T, Enjo K. 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. doi: 10.1007/s10637-014-0130-5. Epub 2014 Jul 1. PMID: 24981575.
In vitro protocol:
1. Wangtrakuldee P, Adeniji AO, Zang T, Duan L, Khatri B, Twenter BM, Estrada MA, Higgins TF, Winkler JD, Penning TM. A 3-(4-nitronaphthen-1-yl) amino-benzoate analog as a bifunctional AKR1C3 inhibitor and AR antagonist: Head to head comparison with other advanced AKR1C3 targeted therapeutics. J Steroid Biochem Mol Biol. 2019 Sep;192:105283. doi: 10.1016/j.jsbmb.2019.01.001. Epub 2019 Jan 11. PMID: 30641225; PMCID: PMC6625945. 2. Kikuchi A, Furutani T, Azami H, Watanabe K, Niimi T, Kamiyama Y, Kuromitsu S, Baskin-Bey E, Heeringa M, Ouatas T, Enjo K. 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. doi: 10.1007/s10637-014-0130-5. Epub 2014 Jul 1. PMID: 24981575.
In vivo protocol:
1. Kikuchi A, Furutani T, Azami H, Watanabe K, Niimi T, Kamiyama Y, Kuromitsu S, Baskin-Bey E, Heeringa M, Ouatas T, Enjo K. 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. doi: 10.1007/s10637-014-0130-5. Epub 2014 Jul 1. PMID: 24981575.
1: Crespo B, Illera JC, Silvan G, Lopez-Plaza P, Herrera de la Muela M, de la Puente Yagüe M, Diaz Del Arco C, Illera MJ, Caceres S. Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple- Negative Breast Cancer Cell Lines. Int J Mol Sci. 2024 Jan 25;25(3):1471. doi: 10.3390/ijms25031471. PMID: 38338747; PMCID: PMC10855276. 2: Crespo B, Caceres S, Silvan G, Illera MJ, Illera JC. The inhibition of steroid hormones determines the fate of IPC-366 tumor cells, highlighting the crucial role of androgen production in tumor processes. Res Vet Sci. 2023 Aug;161:1-14. doi: 10.1016/j.rvsc.2023.05.014. Epub 2023 Jun 1. Erratum in: Res Vet Sci. 2024 Sep;177:105369. doi: 10.1016/j.rvsc.2024.105369. PMID: 37290206. 3: Jamrozik M, Piska K, Bucki A, Koczurkiewicz-Adamczyk P, Sapa M, Władyka B, Pękala E, Kołaczkowski M. In Silico and In Vitro Assessment of Carbonyl Reductase 1 Inhibition Using ASP9521-A Potent Aldo-Keto Reductase 1C3 Inhibitor with the Potential to Support Anticancer Therapy Using Anthracycline Antibiotics. Molecules. 2023 Apr 27;28(9):3767. doi: 10.3390/molecules28093767. PMID: 37175180; PMCID: PMC10180078. 4: Yu X, Yan J, Li Y, Cheng J, Zheng L, Fu T, Zhu Y. Inhibition of castration- resistant prostate cancer growth by genistein through suppression of AKR1C3. Food Nutr Res. 2023 Jan 31;67. doi: 10.29219/fnr.v67.9024. PMID: 36794010; PMCID: PMC9899042. 5: Phoo NLL, Dejkriengkraikul P, Khaw-On P, Yodkeeree S. Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death. Int J Mol Sci. 2021 Nov 19;22(22):12512. doi: 10.3390/ijms222212512. PMID: 34830394; PMCID: PMC8623627. 6: Wangtrakuldee P, Adeniji AO, Zang T, Duan L, Khatri B, Twenter BM, Estrada MA, Higgins TF, Winkler JD, Penning TM. A 3-(4-nitronaphthen-1-yl) amino- benzoate analog as a bifunctional AKR1C3 inhibitor and AR antagonist: Head to head comparison with other advanced AKR1C3 targeted therapeutics. J Steroid Biochem Mol Biol. 2019 Sep;192:105283. doi: 10.1016/j.jsbmb.2019.01.001. Epub 2019 Jan 11. PMID: 30641225; PMCID: PMC6625945. 7: Kikuchi A, Furutani T, Azami H, Watanabe K, Niimi T, Kamiyama Y, Kuromitsu S, Baskin-Bey E, Heeringa M, Ouatas T, Enjo K. 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. doi: 10.1007/s10637-014-0130-5. Epub 2014 Jul 1. PMID: 24981575. 8: Loriot Y, Fizazi K, Jones RJ, Van den Brande J, Molife RL, Omlin A, James ND, Baskin-Bey E, Heeringa M, Baron B, Holtkamp GM, Ouatas T, De Bono JS. Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi- centre phase I/II study. Invest New Drugs. 2014 Oct;32(5):995-1004. doi: 10.1007/s10637-014-0101-x. Epub 2014 Apr 27. PMID: 24771350.