SRC-family and other off-target kinases (SFKs)

The SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases, including SRC, FYN, and LYN, that serve as critical mediators of intracellular signal transduction (UniProt P12931). These enzymes regulate essential cellular processes such as proliferation, differentiation, adhesion, and migration by phosphorylating specific tyrosine residues on target proteins (PubMed: 15546873). In oncology, SFKs are frequently overexpressed or hyperactivated, contributing to the progression of solid tumors and leukemias (PubMed: 16461306). The term 'off-target kinases' refers to the unintended inhibition of these or other kinases by drugs designed for a primary target, such as BCR-ABL or EGFR (PubMed: 18183025). Multi-kinase inhibitors like dasatinib and bosutinib are known to potently inhibit SFKs, which can provide additional therapeutic benefits but also leads to distinct side effects (FDA: Sprycel Label). For instance, the inhibition of SFKs in the pulmonary endothelium is thought to contribute to the development of pleural effusion (PubMed: 20660291). Understanding the broad inhibitory profile of these drugs is vital for predicting clinical outcomes and managing toxicity in patients (PubMed: 24091325). SFKs also play significant roles in immune cell signaling, making them potential targets for inflammatory and autoimmune conditions (PubMed: 11114311).

Other names

SFKNon-receptor tyrosine kinasesSrc familySecondary kinase targets

ATP-competitive inhibition of the catalytic kinase domain, preventing the phosphorylation of tyrosine residues on substrate proteins.