How two researchers at University Michigan — Tomasz Cierpicki, Ph.D., and Jolanta Grembecka, Ph.D. — discovered and developed potent and selective drug-like molecules to treat acute leukemia using biochemical and cell-based assays, and in vivo models. The presentation will cover the key steps that made the project successful.

<strong>About the research</strong>
Chromosomal translocations of the MLL gene, which result in expression of MLL fusion proteins, are found in acute leukemia affecting both children and adults. The MLL rearranged leukemias are particularly prevalent in infants, constituting up to 80% of acute leukemia cases in infants. The oncogenic activity of MLL fusion proteins in critically dependent on their direct interaction with menin, and therefore the menin-MLL interaction represents an attractive target for therapeutic intervention.

The researchers developed very potent small molecules that specifically bind to menin with low nanomolar affinities and inhibit the menin-MLL interaction in vitro and in human cells. They also optimized drug-like properties of these compounds making them suitable for in vivo studies. These compounds demonstrate strong and specific effect in MLL leukemia cells and block progression of MLL leukemia in vivo in mice without affecting normal hematopoiesis.

Their efforts have strong potential to result in development of new anti-cancer agents for acute leukemias with MLL translocations. In this presentation, we will summarize key stages of this project and emphasize critical steps that turned out to be instrumental to successful development of the optimized menin-MLL inhibitors with in vivo efficacy.

<strong>About the speakers</strong>
Tomek Cierpicki, Ph.D. and Jolanta Grembecka, Ph.D. are scientific leaders in targeting the menin-MLL interaction. They have licensed their promising class of compounds to Kura Oncology with the goal of translating the science carried out a U-M into clinical trials patients with acute leukemias and other cancers.