ASP-9521

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. (In Vitro) :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. (In Vivo) :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.

1126084-37-4

ASP9521 | AKR1C3 inhibitor | 17HSD5 inhibitor

>98% (HPLC)

DMSO : ≥ 300 mg/mL 907.94 mM

CC (C) (CC1CCN (CC1) C (=O) c1cc2c ([nH]1) ccc (c2) OC) O

C19H26N2O3

330.32

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.