New anti-cancer ‘degrader’ targets protein key to childhood leukemia

Scientists at the Van Andel Institute and the Icahn School of Medicine at Mount Sinai have developed a powerful anticancer compound that inhibits the growth of cancer cells in a hard-to-treat type of childhood leukemia. The findings are published in the journal Scientific progress.

The MS-41 compound targets and destroys ENL, a protein critical to the progression of MLL-rearranged leukemia. Without ENL, leukemia cells lose their ability to proliferate and spread.

“Up to 80% of acute leukemias in infants are linked to problems with the MLL gene, but there are few effective treatments for MLL-rearranged leukemias,” said Hong Wen, Ph.D., co-corresponding author of a study describing the findings.

“MS-41 is a novel investigational compound that effectively targets and degrades a central survival mechanism in leukemia cells. Our initial results are promising and we are excited to continue developing MS-41 as a potential treatment for leukemia.”

MS-41 belongs to a family of anticancer compounds called PROTAC degraders, which are an increasingly popular approach in cancer drug development.

Unlike traditional small molecule inhibitors, PROTAC degraders completely eliminate their target proteins, allowing them to produce robust therapeutic effects at low doses with fewer side effects. PROTAC degraders also often require less frequent treatment than other currently available anticancer drugs.

The results also reveal that MS-41 did not damage healthy cells when tested in mouse models. These compounds are attractive as drugs because they are less likely to cause side effects.

In the future, Wen and colleagues will study MS-41 in additional models to assess whether it is applicable to other types of ENL-related acute leukemias and other types of cancer such as Wilms tumor.