CEP3891

CEP3891 is a potent and selective small molecule inhibitor of Checkpoint kinase 1 (Chk1), originally developed by Cephalon (now part of Teva). Chk1 is a critical serine/threonine kinase in the DNA damage response (DDR) pathway, where it regulates cell cycle checkpoints (particularly S and G2/M) and DNA repair. By inhibiting Chk1, CEP3891 prevents cancer cells from arresting the cell cycle to repair DNA damage, thereby sensitizing them to DNA-damaging agents or inducing apoptosis through mitotic catastrophe. Preclinical research, particularly in multiple myeloma, has demonstrated that CEP3891 can work synergistically with MEK1/2 inhibitors to downregulate the anti-apoptotic protein Mcl-1 and upregulate the pro-apoptotic protein Bim. This dual inhibition strategy is designed to overcome resistance to conventional therapies like bortezomib by disabling cytoprotective survival signals in malignant cells.