ASP-9521

• CAT Number: I013440
• CAS Number: 1126084-37-4
• Molecular Formula: C19H26N2O3
• Molecular Weight: 330.42
• Purity: ≥95%
• Synonyms: [4-(2-hydroxy-2-methylpropyl)piperidin-1-yl]-(5-methoxy-1H-indol-2-yl)methanone
• InChI: 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
• InChIKey: OXSCPDKUZWPWFR-UHFFFAOYSA-N
• SMILES: CC(C)(CC1CCN(CC1)C(=O)C2=CC3=C(N2)C=CC(=C3)OC)O

ASP-9521 is a potent, selective and orally available AKR1C3 inhibitor with an IC50 of 11 nM for human AKR1C3.
AKR1C3 is a promising therapeutic target in castrationresistant prostate cancer, as combination of an AKR1C3 inhibitor and a gonadotropin-releasing hormone analogue may lead to complete androgen blockade.ASP-9521 inhibits conversion of androstenedione (AD) into androstenediol and testosterone (T) by recombinant human or cynomolgus monkey AKR1C3 in a concentrationdependent manner (IC50, human: 11 nM; IC50,monkey: 49 nM). ASP-9521 shows more than 100-fold selectivity for AKR1C3 over the isoform AKR1C2. In LNCaP-AKR1C3 cells, ASP-9521 suppresses AD-dependent PSA production and cell proliferation[1].
In CWR22R xenografts, single oral administration of ASP-9521 (3 mg/kg) inhibits AD-induced intratumoural T production and this inhibitory effect is maintained for 24 h. After oral administration, ASP-9521is rapidly eliminated from plasma, while its intratumoural concentration remained high. The bioavailability of ASP-9521 after oral administration (1 mg/kg) is 35 %, 78 % and 58 % in rats, dogs and monkeys, respectively[1].

Reference

[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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