University of Michigan

Kura Oncology, Inc.

Szymon Klossowski

Jolanta Grembecka

Tomasz Cierpicki

Dmitry Borkin

Jing Deng

Hao Li

Pingda Ren

Liansheng Li

Tao Wu

Jonathan Pollock

EunGi Kim

Hongzhi Miao

Trupta Purohit

Yi Wang

Dong Chen

Yi Liu

Jun Feng

Deanna Montgomery

David Rogawski

Zhuang Jin

Marta Krotoska

Jin Zhuang

Marta Szewczyk

Provided herein are small molecules comprising a first domain that binds to ASH1L and a second domain that facilitates ASH1L degradation. In particular, ASH1L-targeting proteolysis targeting chimeras (PROTACs) and methods of use thereof for the treatment of disease (e.g., acute leukemia, solid cancers and other diseases dependent on activity of ASH1L) are provided.

ASH1L degraders and methods of treatment therewith

Provided herein are small molecule inhibitors of ASH1L activity and small molecules that facilitate ASH1L degradation and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

ASH1L inhibitors and methods of treatment therewith

Provided herein are small molecules that bind to ASH1L and inhibit ASH1L activity, and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

The present disclosure provides methods of inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins with compositions of Formula (II-A). The methods are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin. Compositions of Formula (II-A) for use in these methods are also provided. 

Substituted inhibitors of menin-MLL and methods of use

The present disclosure provides compounds of Formula (I-A) for inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The compounds are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin. 

Bridged bicyclic inhibitors of menin-MLL and methods of use

The present disclosure provides compounds of Formula (II-A), which inhibit the interaction of menin with one or more of MLL1, MLL2 and MLL-fusion oncoproteins. Also disclosed are methods for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin.

The present disclosure provides compounds of Formula (I-E) for inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The compounds are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin. 

The present disclosure provides compositions and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The compositions and methods of use are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin.

Growing community of inventors

Ann Arbor, MI, United States of America

Szymon Klossowski