SM08502 + FOLFIRI

SM08502 + FOLFIRI is a combination therapy under investigation for the treatment of colorectal cancer and potentially other gastrointestinal cancers. The regimen combines SM08502, a small molecule CDC-like kinase (CLK) and dual-specificity tyrosine-regulated kinase (DYRK) inhibitor designed to modulate RNA splicing by inhibiting these kinases, with FOLFIRI—a well-established chemotherapy combination consisting of folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan. FOLFIRI targets rapidly dividing cancer cells primarily through two mechanisms: - Fluorouracil (5-FU) acts as an antimetabolite, disrupting DNA and RNA synthesis via thymidylate synthase inhibition and RNA/DNA incorporation, resulting in cell death. - Irinotecan is a topoisomerase I inhibitor, leading to DNA damage and apoptosis. - Folinic acid (leucovorin) enhances the effect of 5-FU by stabilizing its binding to thymidylate synthase. SM08502 is being developed to enhance the effect of standard chemotherapy by modulating splicing pathways important for cancer progression. The combination is in clinical trials for colorectal cancer.