fig1

Figure 1. Point mutations within the ALK tyrosine kinase domain and their functional impact. Schematic representation of the ALK tyrosine kinase domain (residues 1116-1183), illustrating the location and functional consequences of representative resistance-associated mutations. The gatekeeper mutation L1196M impairs drug binding. Mutations such as G1202R, S1206Y, and G1269A reduce inhibitor affinity at the ATP-binding pocket. Variants including I1171T/N, F1174C/L/V, R1275Q, and L1152R/P increase ATP binding and stabilize the active kinase conformation. Substitutions at C1156 (C1156Y/L/F) enhance ALK kinase activity, further promoting resistance. Created in BioRender. Long, M. (2025). https://BioRender.com/4hhix6x. ALK: Anaplastic lymphoma kinase; ATP: adenosine triphosphate.