Abelson murine leukemia viral oncogene homolog 1 and Proto-oncogene tyrosine-protein kinase Src (ABL1/SRC)

Abelson murine leukemia viral oncogene homolog 1 (ABL1) and Proto-oncogene tyrosine-protein kinase Src (SRC) are non-receptor tyrosine kinases that function as critical mediators in signal transduction pathways governing cell growth, survival, adhesion, and migration [1.1.1, 1.2.1]. ABL1 is primarily recognized for its role in the BCR-ABL1 fusion protein, the driver of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) [1.1.2, 1.5.3]. SRC is the prototypical member of the Src family kinases (SFKs) and is frequently overexpressed or hyperactivated in various solid tumors and hematological malignancies, where it promotes invasion and metastasis [1.2.5, 1.5.4]. Dual ABL/SRC inhibitors, such as dasatinib and bosutinib, were developed to provide more potent inhibition of BCR-ABL1 and to overcome resistance mechanisms associated with first-generation inhibitors like imatinib [1.4.1, 1.4.2]. These drugs typically act as ATP-competitive inhibitors, blocking the catalytic activity of both proteins to disrupt redundant signaling networks and induce apoptosis in malignant cells [1.4.4, 1.4.5]. While highly effective, these agents are associated with notable safety concerns, including pleural effusion, myelosuppression, and gastrointestinal distress [1.1.4, 1.4.3].

Other names

c-AblJTK7p150c-SrcASVSRC1p60-SrcAbl-Src

ATP-competitive inhibition of the tyrosine kinase domain