University of Michigan

Kura Oncology, Inc.

Cellerant Therapeutics, Inc.

Dmitry Borkin

Jolanta Grembecka

Tomasz Cierpicki

Pingda Ren

Liansheng Li

Tao Wu

Jonathan Pollock

Szymon Klossowski

Yi Liu

Jun Feng

Duxin Sun

Yi Wang

Xiaoqin Li

Jay L Hess

Hongzhi Miao

Jagath Reddy Junutula

Kevin Lloyd Greenman

Mohamed Ibrahim

Hao Li

Jing Deng

Sanjeevani Ghone

Deanna Montgomery

Artem Plekhov

Sylvia Degrado

Sean W Smith

David Rogawski

Zhuang Jin

Marta Krotoska

Jin Zhuang

Marta Szewczyk

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

The present disclosure provides compounds and methods for inhibiting the interaction of menin with its upstream or downstream signaling molecules including but not limited to MLL1, MLL2 and MLL-fusion oncoproteins. Compounds of the disclosure may be used in methods for the treatment of a wide variety of cancers and other diseases associated with one or more of MLL1, MLL2, MLL fusion proteins, and menin.

Thienopyrimidine and thienopyridine compounds and methods of use thereof

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 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.

Methods and compositions for inhibiting the interaction of menin with MLL proteins

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. 

Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.

Isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers

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 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.

Growing community of inventors

Ann Arbor, MI, United States of America

Dmitry Borkin