SIC-19

SIC-19 is a potent and highly selective small molecule inhibitor of **salt-inducible kinase 2 (SIK2)**. It works by promoting SIK2 protein degradation through the ubiquitination-proteasome pathway. SIC-19 exhibits **synthetic lethality** when used in combination with **PARP inhibitors**—notably enhancing the efficacy of PARP inhibitors by suppressing homologous recombination (HR) DNA repair. The drug impairs phosphorylation and nuclear translocation of RAD50, diminishes HR-mediated repair, potentiates DNA damage, and induces apoptosis in cancer cells. Significant antitumor effects have been shown in ovarian cancer, triple-negative breast cancer (TNBC), and pancreatic cancer models, especially when paired with PARP inhibitors like olaparib or niraparib. Primary indications are preclinical and translational research in ovarian cancer, TNBC, and pancreatic cancer, focusing on overcoming resistance to PARP inhibitors. Developed through compound library screening and structure-guided drug design, SIC-19's developer and main supplier appears to be Probechem Biochemicals.

Brand names

SIC-19SIC19SIC 19

Other names

SIC-19SIC19SIC 19