Tyrosine-protein kinase group (FLT3, Lck, Lyn, Src) (Multi-kinase)

This target profile represents a group of tyrosine kinases, including the receptor tyrosine kinase FLT3 and the non-receptor Src family kinases (Lck, Lyn, and Src). These proteins are essential components of cellular signaling pathways that regulate growth, survival, and differentiation. Fms-like tyrosine kinase 3 (FLT3) is critical for hematopoietic development, and its mutations are frequently implicated in the pathogenesis of acute myeloid leukemia (AML) (UniProt: P36888). The Src family kinases (SFKs), such as Lck, Lyn, and Src, act as intracellular signaling hubs that relay signals from various cell surface receptors to the nucleus (UniProt: P12931, P06239, P07948). Dysregulation of these kinases, often through overexpression or constitutive activation, is a common feature in many hematologic and solid malignancies. Multi-kinase inhibitors like dasatinib, midostaurin, and ponatinib target these enzymes by binding to their ATP-binding domains, thereby blocking downstream oncogenic signaling (FDA Label: Dasatinib, Midostaurin). These drugs are widely used in the treatment of leukemias, including CML and AML, where they have significantly improved patient outcomes. However, the broad inhibition of multiple kinases can lead to significant systemic toxicities, such as myelosuppression and cardiotoxicity, necessitating careful clinical management (StatPearls: Tyrosine Kinase Inhibitors). Monitoring for specific mutations, such as FLT3-ITD, is essential for selecting patients who will benefit most from these therapies.

Other names

Fms-like tyrosine kinase 3 (FLT3)Lymphocyte-specific protein tyrosine kinase (Lck)Lck/Yes-related novel tyrosine kinase (Lyn)Proto-oncogene tyrosine-protein kinase Src (Src)Src family kinases (SFK)Receptor-type tyrosine-protein kinase FLT3STK1CD135p56lckp53lyn

These kinases are inhibited through ATP-competitive binding within the catalytic kinase domain, which prevents the phosphorylation of tyrosine residues on downstream signaling proteins and effectively halts oncogenic pathways such as PI3K/Akt, MAPK/ERK, and STAT5 (PubMed: PMC4915101).