Dana-farber-cancer Institute Inc.

Harvard College

The General Hospital Corporation

Acetylon Pharmaceuticals, Inc.

Immunogen, Inc.

Biotest Ag

Teru Hideshima

Kenneth Carl Anderson

Ralph Mazitschek

Stephen J Haggarty

Stuart L Schreiber

James Elliott Bradner

Nicholas Paul Kwiatkowski

Steven N Quayle

Simon Stewart Jones

Jared T Shaw

Edward Franklin Greenberg

Constantine S Mitsiades

Balaram Ghosh

Nicholas Mitsiades

Nathanael Schiander Gray

Benjamin Daelken

Sara Jean Buhrlage

Nathanael S Gray

Frank Osterroth

Christoph Bruecher

Christoph Uherek

Matthias Germer

Silke Aigner

Francesca Cottini

Xiaoxi Liu

Gullu Gorgun

The present disclosure relates to a pharmaceutical combination comprising (a) a histone deacetylase inhibitor and (b) a CD38 inhibitor, FIG.A including combined preparations and pharmaceutical compositions thereof; uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Pharmaceutical combinations comprising a histone deacetylase inhibitor and a CD38 inhibitor and methods of use thereof

The present disclosure relates to a pharmaceutical combination comprising (a) a histone deacetylase 6 inhibitor and (b) a programmed death ligand 1 (PD-L1) inhibitor, including combined preparations and pharmaceutical compositions thereof; uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Pharmaceutical combinations comprising a histone deacetylase inhibitor and a programmed death-ligand 1 (PD-L1) inhibitor and methods of use thereof

The present invention relates to compounds which inhibit histone deacetylase activity and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to methods of treating and preventing hematological cell proliferative disorders, such as multiple myeloma, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Inhibitors of histone deacetylase

The application relates to a compound of Formula (I) which modulate the amount of STK4, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of STK4. 

Compounds for the degradation of STK4 and treatment of hematologic malignancies

The present disclosure relates to a pharmaceutical combination comprising (a) a histone deacetylase inhibitor and (b) a CD38 inhibitor, including combined preparations and pharmaceutical compositions thereof; uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

The invention provides, inter alia, methods of prognosing the survival of a multiple myeloma patient based levels of TP53RK in multiple myeloma cells of the patient. Also provided are methods of screening for therapeutic agents for treating multiple myeloma based on their ability to decrease TP53RK levels or activity in a patient with multiple myeloma.

Compositions and methods for treating multiple myeloma

The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC/TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

Treatment of protein degradation disorders

The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, polymorphs, and compositions thereof. Also provided are methods and kits involving the inventive compounds for treating proliferative diseases (e.g., cancers (e.g., breast cancer, prostate cancer, lung cancer, and ovarian cancer), benign neoplasms, angiogenesis, inflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound of the invention may enhance the anti-tumor immune response by inhibiting or eliminating the immune suppression mediated by immune suppressor myeloid cells (MDSCs), inducing apoptosis, and/or inhibit or down-regulate proteins (e.g., epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), X-linked inhibitor of apoptosis protein (XIAP), and heat shock protein 90 (Hsp90)) in the subject. 

Anti-proliferative compounds and uses thereof

Disclosed are immunoconjugates having specificity for CD138 that diminish adhesion of CD138 expressing tumor cells to stroma cells and methods of using the same. This diminished adhesion renders the tumor cells not only susceptible to the immunoconjugate, but also to other agents, in particular cytotoxic agents.

Methods and agents for improving targeting of CD138 expressing tumor cells

The present invention relates to therapeutic compositions for treating cancer or preventing the growth of cancer cells, e.g., tumor growth, in a subject. The present invention also relates to methods for treating cancer, e.g., inhibiting tumor growth, in a subject who has become resistant to treatment, by administering to a subject an effective amount of a proteasome inhibitor and an effective amount of a therapeutic agent, e.g., a chemotherapeutic agent. The present invention further relates to methods for purging bone marrow, i.e., removing cancer cells from bone marrow, by exposing the bone marrow cells to a proteasome inhibitor and a therapeutic agent, e.g., a chemotherapeutic agent.

Methods and compositions for treating cancer using proteasome inhibitors

Growing community of inventors

Brookline, MA, United States of America

Teru Hideshima