Novel small-molecule therapy shows promise against deadly pediatric leukemia

Researchers at Mount Sinai have developed a therapy that shows promise against fatal childhood leukemia. The small-molecule therapy was highly effective in combating a type of acute myeloid leukemia in both in vitro and in vivo experiments, according to research published in September in Science Translational Medicine.

The therapy, called MS67, causes the breakdown of the WDR5 protein, which stimulates the proliferation of acute myeloid leukemia with a specific genetic makeup called mixed lineage leukemia rearrangement. This type of leukemia is more common in children, responds very poorly to standard treatments and has a bleak prognosis, and has so far confused researchers.

WDR5 also plays an important role in stimulating the proliferation of other cancers, such as pancreatic cancer, so researchers believe it is likely that small molecule WDR5 degraders, such as MS67, could also be effective in treating those cancers.

This study is the first to demonstrate that pharmacologic degradation of WDR5, which selectively eliminates the protein, is an effective and superior therapeutic strategy than pharmacologic inhibition or blockade of WDR5 for the treatment of WDR5-dependent cancers, including mixed-lineage acute myeloid leukemia. leukemia rearrangement. In addition, MS67 is the first WDR5 small molecule degrader to exhibit robust antitumor activities in vivo.”

Jian Jin, PhD, the Mount Sinai Professor in Therapeutics Discovery and Director of the Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai

The research team led by Dr. jin; Greg Wang, PhD, of the University of North Carolina at Chapel Hill; and Aneel Aggarwal, PhD, professor of pharmacological and oncological sciences, at the Tisch Cancer Institute at Mount Sinai, discovered MS67, a new highly potent and selective small molecule degrader of WDR5, which effectively suppressed the growth of this type. acute myeloid leukemia cells derived from patients both in vitro and in vivo, using cancer cells from patients in mouse models. Using a battery of biochemical, biophysical, structural, cellular, genomic and in vivo studies, the research team showed that MS67 is a much better therapeutic agent than other therapies that inhibit rather than break down WDR5.


Mount Sinai Health System

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