Allosteric en-ABL-ement

Novartis AG has developed a new strategy to prevent leukemias from becoming resistant to its CML drugs against BCR-ABL. Rather than combining the inhibitors with other classes of cancer therapies, the company is doubling its attack on the target with compounds that hit the allosteric and catalytic sites.

Novartis markets Gleevec imatinib and Tasigna nilotinib to treat chronic myelogenous leukemia (CML) and other hematologic malignancies. Although the drugs revolutionized treatment of the disease, they both target the catalytic site of BCR-ABL, and are vulnerable to resistance mutations that can arise in the site, causing patients to relapse...