Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia.

摘要: Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, who have progressed to advanced-stage frequently fail respond or lose their response owing emergence of drug-resistant mutants protein. More than 40 such point mutations been observed in imatinib-resistant patients. The crystal structures wild-type and mutant complex other small-molecule inhibitors were determined, aim understanding molecular basis resistance aid design optimization active against mutants. These are presented way illustrates approaches used generate multiple structures, type information that can be gained this is support drug discovery.