Fig 3. Synthesis and hydrolysis of AL776, the lead K1-K2 prototype targeting EGFR and c-Src.

The synthesis of AL776 was carried out in our laboratory according to the steps indicated above. The resulting type III K1-K2 molecule is designed to undergo hydrolysis inside the cells and release a potent EGFR tyrosine kinase inhibitor (K1) termed AL621 and a potent c-Src tyrosine kinase inhibitor (K2) dasatinib (type I). AL776 is also capable of exerting its dual inhibitory property by directly interacting with each target as an intact molecule (type II).