ANTI-TUMOR MULTIDRUG RESISTANCE OF HETEROARYL AMIDE COMPOUND, USE IN TREATMENT OF CANCERS AND PROTEIN-DRUG MOLECULAR COMPLEX

摘要

Disclosed are an anti-tumor multidrug resistance of a heteroaryl amide compound as a microtubule inhibitor, the use in the treatment of cancers and a protein-drug molecular complex. High throughput drug screening using cells transformed by oncogenic RAS identifies a lead heteroaryl amide compound blocking cell proliferation. Analysis of the structure-activity relationship indicates that the skeleton (taking I-28 as an example) of the series is an effective inhibitor for tumor cell growth. Further analysis indicates that such a compound exhibits good pharmacological properties of anti-tumor MDR both in vitro and in vivo. In conclusion, a novel skeleton represented by I-28 can be developed as a cancer therapeutic agent, specifically for tumor multiple resistance.