BRD9500 is an orally active phosphodiesterases 3 (PDE3) inhibitor with IC50s of 10 and 27 nM for PDE3A and PDE3B, respectively. Antitumor activity[1].
BRD9500 is a DNMDP analog. DNMDP potently and selectively inhibits PDE3A and PDE3B and kills cancer cells by inducing PDE3A/B interactions with SFLN12[1]. BRD9500 exhibits an EC50 of 1 nM for SK-MEL-3 melanoma cell line viability[1]. BRD9500 exhibits an EC50 of 1.6 nM for HeLa viability[1].BRD9500 (10 μM; 8 hours) stabilizes the PDE3A-SLFN12 interaction in HeLa cells[1]. Western Blot Analysis[1] Cell Line: HeLa cells
BRD9500 (10, 20, and 50 mg/kg; orally) inhibits SK-MEL-3 melanoma growth in mice[1].BRD9500 shows high plasma levels in mice after iv (1 mg/kg) as well as po (2 mg/kg) dosing over eight hours making it a valuable candidate for in vivo xenograft testing[1]. Animal Model: Female NMRI nude mice bearing SK-MEL-3 melanoma cells tumor xenografts[1]
[1]. Timothy A Lewis, et al. Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing. ACS Med Chem Lett. 2019 Oct 18;10(11):1537-1542.