I-12

I-12 is a novel piperazinylpyrimidine derivative developed as a multi-kinase inhibitor for the potential treatment of cancer. Designed by researchers at the University of the Pacific, the compound features a piperazinylpyrimidine core attached to kinase-privileged fragments. Preclinical profiling using KINOMEscan™ technology has demonstrated that I-12 primarily targets the platelet-derived growth factor receptor (PDGFR) tyrosine kinase subfamily, including KIT (and its D816V mutant), FLT3, PDGFRA, PDGFRB, and CSF1R. It also exhibits strong binding to CDK11 and modest inhibitory activity against DDR1 and CSNK1D. In vitro studies have shown that I-12 possesses selective cytotoxic activity against various cancer cell lines within the NCI-60 panel, maintaining a significant safety margin with a mean GI50 of 5.25 μM and an LC50 exceeding 100 μM. The compound also adheres to Lipinski's rule of five, suggesting favorable drug-like properties.