WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205818
CAS#: 1126084-37-4
Description: 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.
MedKoo Cat#: 205818
Name: ASP9521
CAS#: 1126084-37-4
Chemical Formula: C19H26N2O3
Exact Mass: 330.19434
Molecular Weight: 330.42
Elemental Analysis: C, 69.06; H, 7.93; N, 8.48; O, 14.53
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
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 52.26 | 158.16 | |
| DMF | 10.0 | 30.26 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.51 | |
| Ethanol | 36.35 | 110.01 |
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.
| 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: 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 Jul 1. [Epub ahead of print] PubMed PMID: 24981575.
2: 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 Apr 27. [Epub ahead of print] PubMed PMID: 24771350.
