Dasatinib

Dasatinib, also known as BMS-354825 is a highly potent, ATP competitive, orally active dual SRC (proto-oncogene tyrosine kinase SRC)/Bcr-Abl inhibitor with potent antitumor activity. Dasatinib also induces autophagy and apoptosis and it has been approved for the treatment of hematologic tumors. SRC (proto-oncogene tyrosine kinase SRC), also known as c-SRC, belongs to the non-receptor tyrosine kinase (SFK) protein family. It is involved in embryonic development, cell growth, adhesion, migration, differentiation, and apoptosis. It is present in an inactive conformation until activated by adhesion receptors, receptor tyrosine kinases such as EGFR (epidermal growth factor receptor) and PDGFR (platelet-derived growth factor receptor), G-protein coupled receptors, and cytokine receptors. Phosphorylation at Tyr527 by CSK/MATK (C-terminal Src kinase) or ChK (CSK homolog kinase) and dephosphorylation at Tyr416 by phosphatases leads to its activation. Once active it phosphorylates its substrates, which include PI3Ks (phosphoinositide 3-kinases), cytoskeleton proteins, channel proteins and metabolic enzymes, participating in multiple pathways. It is a proto-oncogene, with overexpression and overactivation resulting from mutations, increased expressions of its activators or decrease of its inactivators, being found in glioblastoma (GBM), lung, liver, breast, bladder cancer, and others. Several inhibitors of this protein have been studied, and Dasatinib has been approved for treatment of hematologic tumors. However, the possible side effects and development of drug resistance have been a concern. The development of new therapeutic strategies towards this protein will bring advances into oncology.