ASP9521

Description: ASP9521 is a novel, selective, orally bioavailable inhibitor of 17beta-hydroxysteroid dehydrogenase type 5 (17betaHSD5; 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, 11 nmol/L; ?IC50, 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.

References: 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 ASP952 a novel, selective, orally bioavailable inhibitor of 17beta-hydroxysteroid dehydrogenase type 5 (17betaHSD5; AKR1C3). Invest New Drugs. 2014 Jul 1. Epub ahead of print PubMed PMID: 24981575.