Src family kinases and Abelson murine leukemia viral oncogene homolog 1 (SFK/ABL1)

Src family kinases (SFKs) and ABL1 are non-receptor tyrosine kinases that play critical roles in regulating cellular processes such as growth, survival, and adhesion. SFKs, including members like c-Src, Fyn, and Lyn, are often overexpressed or hyperactivated in various solid tumors and hematologic malignancies, contributing to tumor progression and metastasis. ABL1 is most notably recognized for its role in the BCR-ABL1 fusion protein, the primary driver of chronic myeloid leukemia (CML). Because SFKs and ABL1 share structural similarities and often cooperate in oncogenic signaling pathways, they are frequently targeted simultaneously by multi-kinase inhibitors. Drugs like dasatinib and bosutinib are designed to bind the ATP-binding pockets of both SFKs and ABL1, effectively disrupting the signaling cascades that promote leukemic cell proliferation and survival. This dual targeting approach is particularly effective in overcoming resistance to first-generation ABL inhibitors and managing advanced stages of Philadelphia chromosome-positive leukemias.

Other names

Src/AblSFK/ABLc-Src/c-AblProto-oncogene tyrosine-protein kinase Src and ABL1Dual Src/Abl kinases

Competitive inhibition of the ATP-binding site of the kinase domain, preventing phosphorylation of downstream substrates and inhibiting oncogenic signaling pathways.