Structure-Guided Discovery of Novel N4-(Substituted Thiazol-2-yl)-N2-(4-Substituted phenyl)pyrimidine-2,4-Diamines as Potent CDK2 and CDK9 Dual Inhibitors with High Oral Bioavailability

exhibited 86.7% oral bioavailability in rats and effectively inhibited tumor growth in HCT116 xenograft and C6 glioma rat models without significant toxicity. Overall, these observations clearly confirmed the promising therapeutic strategy of CDK2/9 dual inhibitors and provided a novel potent candidate for cancer therapy.