SGI-1252

SGI-1252 is a small molecule inhibitor of Janus kinase 2 (JAK2) and activin receptor-like kinase 2 (ALK2), originally developed by SuperGen (now part of Astex Pharmaceuticals). It was designed using the proprietary CLIMB computational drug discovery platform. SGI-1252 demonstrates potent inhibition of wild-type JAK2, the JAK2(V617F) mutation, and JAK1, while sparing JAK3. By blocking the phosphorylation of STAT5 and inhibiting JAK2-dependent antiapoptotic genes, the compound induces apoptosis in JAK2-mutant cell lines. It has been investigated preclinically for the treatment of myeloproliferative disorders, solid tumors (such as pancreatic and lung cancers), and autoimmune diseases, showing oral bioavailability and anti-tumor activity in xenograft models.