Additional dasatinib kinase targets

Additional dasatinib kinase targets refer to the broad array of tyrosine kinases inhibited by dasatinib beyond its primary targets, BCR-ABL and the SRC family. These secondary targets include the Mast/stem cell growth factor receptor (c-KIT), Platelet-derived growth factor receptor beta (PDGFRB), Ephrin type-A receptor 2 (EPHA2), and Discoidin domain receptors 1 and 2 (DDR1/2) [1, 2]. These proteins are integral to various cellular processes, including growth factor signaling, cell-matrix interactions, and angiogenesis [2]. While the inhibition of these additional kinases extends dasatinib's therapeutic utility to conditions like gastrointestinal stromal tumors and systemic mastocytosis, it is also responsible for the drug's unique toxicity profile [3]. For example, the inhibition of PDGFR and SRC family kinases is strongly associated with the development of pleural effusion and fluid retention in patients [1, 3]. Consequently, understanding this multi-kinase profile is essential for both expanding clinical applications and managing the systemic side effects associated with dasatinib therapy [2, 3]. Sources: [1] Sprycel (dasatinib) FDA Prescribing Information; [2] Karaman et al. (2008) Nature Biotechnology; [3] Gupta et al. (2016) Therapeutic Advances in Hematology.

Other names

Secondary dasatinib targetsDasatinib off-targetsDasatinib-sensitive tyrosine kinasesDasatinib kinome

Dasatinib acts as a potent, ATP-competitive inhibitor that binds to both the active and inactive conformations of the kinase domain of its targets, thereby preventing the phosphorylation of downstream signaling proteins [1, 2].