Northwestern University

Ali Shilatifard

Edwin Richard Smith

Lu Wang

Kaiwei Liang

Gary E Schiltz

Rama K Mishra

Zibo Zhao

Kristen Stoltz

Disclosed are methods for methods, compounds, and compositions for treating cancers characterized by therapeutic targeting of the BAP1 histone H2A deubiquitinase (DUB) complex, otherwise referred to herein as the BAP1 complex. In particular, the methods, compounds, and compositions disclosed herein relate to the use of therapeutic agents that inhibit the biological activity of the BAP1 complex for treating cancers such as myeloid neoplasms.

Therapeutic targeting of the BAP1 complex in cancer

Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

Small molecules for disrupting the super elongation complex and inhibiting transcription elongation for cancer therapy

Disclosed are methods and pharmaceutical compositions for treating a cancer in a subject in need thereof, the cancer characterized by proteolytic cleavage by taspase1 of the mixed-lineage leukemia 1 gene product (MLL1), the method comprising administering to the subject a therapeutic agent that inhibits cleavage by taspase1 of MLL1. Suitable therapeutic agents may include agents that inhibit the kinase activity of casein kinase II (CKII). Cancer treated by the disclosed methods and pharmaceutical compositions may include leukemia such as Acute Lymphoblastic Leukemia (ALL) and/or Acute Myeloid Leukemia (AML) and in particular, leukemia characterized by rearrangements in MLL1.

Therapeutic targeting of proteolytic cleavage of the mixed lineage leukemia gene product (MLL1) by taspase1 using kinase inhibitors

Disclosed are methods for treating Set1/COMPASS-associated cancers characterized by expression of Set1B/COMPASS. The methods typically include administering a therapeutic amount of an inhibitor of the Set1B/COMPASS pathway and/or an agonist for a target that is negatively regulated by the Set1B/COMPASS pathway.

Therapeutic targeting of SET1B/compass pathway for treating cancers

Disclosed are methods for treating cancers associated with rearrangements in the mixed lineage leukemia gene (MLL-r), including MLL-r leukemia. The methods typically include administering a therapeutic amount of one or more therapeutic agents that inhibit the biological activity of one or more members of the interleukin-1 signaling pathway such inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4).

Therapeutic targeting of interleukin-1 receptor-associated kinase 4 (IRAK4) in cancers characterized by rearrangements in the mixed lineage leukemia gene (MLL-r)

Therapeutic targeting of the interleukin 1 receptor-associated kinase 4 (IRAK4) in leukemias characterized by rearrangements in the mixed lineage leukemia gene (MLL-r)

Growing community of inventors

Chicago, IL, United States of America

Ali Shilatifard