N

AAL-993 (ZK-260255)

The crystal structure of the drug-protein complex showed that, similar to imatinib, AAL-993 targets the inactive conformation of the enzyme. The binding involves three hydrogen bond interactions (Fig. 9.12) and several hydrophobic interactions. Thus, the phenyl ring of the anthranilamide unit is sandwiched between the hydrophobic side chains of Val-916 and Lys-868, and the trifluoro-methylphenyl substituent fits a lipophilic pocket.26

Vandetanib (ZD6474) belongs to the quinazoline family and is being evaluated in several Phase II clinical trials. Quinazolines were initially developed as EGFR-TK

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