New class of drug could treat leukemia with fewer side effects

Scientists have identified two molecules that could help treat leukemia, in a way that’s far less damaging to healthy cells than existing chemotherapy. The compounds work using a different mechanism that’s more selective for cancerous cells, and importantly, they’re already in use for other purposes.

Abnormal activity in an enzyme called DNMT3A has previously been linked to acute myeloid leukemia, by promoting the formation of abnormal blood cells. Many current chemotherapy drugs work by disabling the DNMT3A enzyme – but unfortunately, they also interfere with the activity of DNMT1, a similar enzyme with vital roles in healthy cells. This causes many of the toxic side effects experienced by patients undergoing chemotherapy.

For the new study, the researchers investigated ways to home in on DNMT3A alone. The enzyme is known to form complexes with partner proteins while it gets to work, so the team scoured a chemical library of existing drugs until they found two that interfere with this partnering-up process.

The two compounds, pyrazolone and pyridazine, target a non-active site on DNMT3A, which works to prevent it from forming complexes and ultimately stops the cascading effects that can lead to leukemia. Importantly, this mechanism means it doesn’t affect DNMT1.

The team says this breakthrough could lay the foundation for a new class of drugs, which could eventually help treat leukemia and other forms of cancer with much less toxicity than existing chemotherapy drugs. However, there’s still plenty of work left to do to uncover how it works in the long-term, and how it could be made even more potent.

Thankfully there is one less roadblock in the way – because the drugs are already in use for other diseases, it should be a more straightforward process to get them approved for use against leukemia.

The research was published in the Journal of Medicinal Chemistry.