The INK4 family members p16INK4a and p15 INK4b negatively regulate cell cycle progression by inhibition of cyclin-dependent kinase (CDK) 4/6. Loss of p16INK4a functional activity is frequently observed in tumor cells, and is thought to be one of the primary causes of carcinogenesis. In contrast, despite the biochemical similarity to p16
INK4a, the frequency of defects in p15INK4b was found to be lower than in p16
INK4a, suggesting that p15
INK4b-inductive agents may be useful for tumor suppression. Here we report the discovery of a novel pyrido-pyrimidine derivative, JTP-70902, which exhibits p15
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