[4-[[5-Fluoro-4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-2-pyrimidinyl]amino]phenyl][(3S)-3-(methylamino)-1-pyrrolidinyl]Methanone

Biological Activity

azd-5597 is a potent cdk inhibitor with ic50 values of 2 nm for cdk1 and cdk2, respectively [1].the cyclin-dependent kinases (cdks) are serine-threonine protein kinases with roles in the regulation of the cell cycle, and also involved in regulating transcription, mrna processing, and the differentiation of nerve cells [1].azd-5597 is a potent imidazole pyrimidine amide cdk inhibitor. in lovo cells, azd-5597 exhibited high level of anti-proliferative activity with ic50 value of 0.039 μm. azd-5597 exhibited excellent aqueous solubility ( > 50 mg/ml), photostability (t1/2 > 24 h), hydrolytic stability (ph 4-10, t1/2 > 100 days), plasma stability ( > 18 h) and the lack of cyp inhibition. the overall profile of azd-5597 indicated that it was suitable for further development as an iv agent [1].in nude mouse and rat, azd-5597 possessed good pharmacokinetic parameters with moderate to low clearance. in nude mice implanted subcutaneously with sw620 human colon adenocarcinoma cells, azd-5597 (15 mg/kg, dosed intermittently for 3 weeks, ip) inhibited tumour volume by 55% [1].

References

jones cd, andrews dm, barker aj, et al. the discovery of azd5597, a potent imidazole pyrimidine amide cdk inhibitor suitable for intravenous dosing. bioorganic & medicinal chemistry letters, 2008, 18(24): 6369-6373.