KC12

KC12 is a pyridopyrimidine derivative developed as a potent and selective dual inhibitor of Provirus Integration in Maloney murine leukemia virus (Pim) kinases and mitogen-activated protein kinase-interacting kinases (Mnk). It was optimized from a predecessor compound, 21o, to improve aqueous solubility and pharmacokinetic properties. KC12 targets the cap-dependent protein translation pathway, which is frequently dysregulated in myeloid leukemias. By concurrently inhibiting Pim and Mnk kinases, KC12 suppresses the phosphorylation of eIF4E and 4EBP1, leading to the downregulation of oncogenic proteins such as c-Myc and Mcl-1. In preclinical studies, KC12 has demonstrated anti-proliferative activity, induction of G0/G1 cell cycle arrest, and apoptosis in leukemia cell lines (K562 and MOLM-13), as well as significant antitumor efficacy in xenograft models.