STF-083010

STF-083010 is a small molecule inhibitor that selectively targets the endonuclease activity of Inositol-requiring enzyme 1 alpha (IRE1α), a key sensor of the unfolded protein response (UPR). By inhibiting the RNase domain of IRE1α, STF-083010 prevents the unconventional splicing of XBP1 mRNA into its active transcription factor form, sXBP1. This blockade disrupts the adaptive capacity of cells to handle endoplasmic reticulum (ER) stress, leading to growth arrest and apoptosis. STF-083010 has demonstrated significant anti-tumor activity in preclinical models of multiple myeloma and pancreatic cancer, both as a monotherapy and in combination with other agents like bortezomib or gemcitabine. It is widely utilized as a chemical probe to study the role of the IRE1-XBP1 pathway in various diseases.