University of Michigan

University of Virginia Patent Foundation

Jay L Hess

Jolanta Grembecka

Tomasz Cierpicki

Duxin Sun

Dmitry Borkin

Xiaoqin Li

Kevin Lloyd Greenman

Zaneta Nikolovska-Coleska

Mohamed Ibrahim

Chenxi Shen

Artem Plekhov

The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 3: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

Compositions comprising thienopyrimidine and thienopyridine compounds and methods of use thereof

The present invention relates to MLL fusion proteins (e.g., AF9 and ENL), which activate target genes in part via recruitment of histone methyltransferase DOT1L. In particular, the present invention provides the AF9/ENL binding site in DOT1L and agents that block the protein-protein interactions between AF9/ENL and DOT1L, therefore inhibiting the activity of DOT1L, and inhibiting MLL-fusion protein associated leukemia.

Compositions and methods relating to hindering DOT1L recruitment by MLL-fusion proteins

The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 4b: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 2: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 4: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

The invention relates generally to effective treatment leukemia. In particular, the present invention provides compositions and methods to inhibit the interaction of menin with MLL and MLL-fusion oncoproteins, and well as systems and methods to screen for such compositions.

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Ann Arbor, MI, United States of America

Jay L Hess