Nature Chemical Biology: Targeting Lipid-Protein Interaction to Treat Syk-Mediated AML

University of Illinois Cancer Center members, along with others at the University of Illinois Chicago and the University of Illinois Urbana-Champaign, reported in Nature Chemical Biology the development of new small molecule inhibitors of lipid-protein interaction (LPI). LPI is a target for new drug development because dysregulated LPI has been linked to diseases, most notably cancer, the study explains.

Wonhwa Cho, PhD, a Cancer Center member in the Cancer Biology research program, is the corresponding author of the pilot study that evaluated the efficacy of lipid–Src homology 2 (SH2) domain interaction inhibitors for spleen tyrosine kinase (Syk), which is implicated in hematopoietic malignancies, including acute myeloid leukemia (AML). The new Syk inhibitor potently and specifically suppressed AML cell lines and patient-derived AML cells and was recalcitrant to drug resistance, which poses a major challenge to kinase-based cancer drug development.

Other Cancer Center members, Nadim Mahmud, MD, PhD, and Irum Khan, MD, of the Translational Oncology Program, also were study authors.

“Our work demonstrates that targeting lipid binding of SH2 domain-containing kinases is a promising new approach to developing new small molecule cancer drugs as numerous oncogenic kinases contain lipid-binding SH2 domains. Our Syk inhibitor represents the first successful development of an LPI inhibitor for kinases. It also shows that LPI can be specifically and potently inhibited by synthetically amenable nonlipid-like small molecules, which will facilitate further LPI drug development” Cho said. 

The study was published on October 13, 2022.

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