Description
BRD9500 is an orally active phosphodiesterases 3 ( PDE3 ) inhibitor with IC 50 s of 10 and 27 nM for PDE3A and PDE3B, respectively. Antitumor activityIn VitroBRD9500 is a DNMDP analog. DNMDP potently and selectively inhibits PDE3A and PDE3B and kills cancer cells by inducing PDE3A/B interactions with SFLN12. BRD9500 exhibits an EC 50 of 1 nM for SK-MEL-3 melanoma cell line viability. BRD9500 exhibits an EC 50 of 1.6 nM for HeLa viability. BRD9500 (10 µM; 8 hours) stabilizes the PDE3A-SLFN12 interaction in HeLa cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: HeLa cells Concentration: 10 µM Incubation Time: 8 hours Result: SLFN12 coimmunoprecipitation was analyzed by immunoblotting with an anti-V5 antibody to detect the SLFN12-V5 fusion protein. The SLFN12-V5 was clearly detected with the anti-V5 antibody.In VivoBRD9500 (10, 20, and 50 mg/kg; orally) inhibits SK-MEL-3 melanoma growth in mice. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female NMRI nude mice bearing SK-MEL-3 melanoma cells tumor xenografts Dosage: 10, 20, and 50 mg/kg Administration: Orally at 10 and 20 mg/kg twice daily (2QD) and at 50 mg/kg once per day (QD). Result: Achieved the strongest antitumor activity at 50 mg/kg. All treatments were well tolerated without critical body weight loss or toxicities.IC50& Target:PDE3A 10 nM (IC 50 ) PDE3B 27 nM (IC 50 )