Selectively inhibiting GSK3's double genes for AML

Researchers at the Broad Institute of MIT and Harvard and colleagues found a way to design highly selective glycogen synthase kinase 3 inhibitors that target one of two forms of the gene. The approach could help treat acute myelogenous leukemia while circumventing toxicities associated with dual inhibition of GSK3 paralogs.

GSK3 is encoded across GSK3 alpha (GSK3A) located on chromosome 19 and GSK3 beta (GSK3B) located on chromosome 3. Previous research suggests both contribute to the development of several diseases, including AML, but little is known about the role of each paralog in disease. Since the genes' amino acid sequences are so similar, targeting just one of them has proven a challenge...