Harvard College

Leland Stanford Junior University

Dana-farber-cancer Institute Inc.

The Broad Institute, Inc.

The General Hospital Corporation

Massachusetts Institute of Technology

Other

New York University

The Scripps Research Institute

Millennium Pharmaceuticals Limited

Howard Hughes Medical Institute

The Board Institute, Inc.

Stuart L Schreiber

Gerald R Crabtree

Peter Belshaw

Thomas J Wandless

David M Spencer

Timothy F Jamison

Christian A Hassig

Steffan Nicholas Ho

Robert F Standaert

Jack Taunton

Gabriel Fenteany

Stephen J Haggarty

Weiping Tang

Christina M Grozinger

Ralph Mazitschek

Douglas A Melton

Alykhan Shamji

Shuibing C Chen

Malgorzata Borowiak

James Elliott Bradner

Kenneth Carl Anderson

Nicholas Paul Kwiatkowski

James Bradner

Teru Hideshima

Jared T Shaw

Steven J Burakoff

Edward Franklin Greenberg

Julia Lamenzo Fox

Lee F Peng

Benito Munoz

Lee L Rubin

Brent R Stockwell

Matthew D Shair

Ramnik Xavier

Partha Pratim Nag

Lance Davidow

Daisuke Ito

Andrew Stern

Zarko Boskovic

Rene Maehr

Julia Lamenzo

Scott M Sternson

Jason C Wong

Kathryn M Koeller

Angela N Koehler

Paul A Clemons

Derek S Tan

Michael A Foley

Mahmud Hussain

Jason Law

Matthias Leiendecker

Ke Liu

Kelvin Lam

Nathanael Schiander Gray

Irving L Weissman

Hwan Geun Choi

Yanke Liang

Li-Huei Tsai

Young-Tae Chang

Theodore M Kamenecka

David Spencer

Mingji Dai

Sara Jean Buhrlage

Michel Weiwer

Timothy J Mitchison

Patrick Griffin

Gavin MacBeath

William C Hahn

Thomas Sundberg

Bridget K Wagner

Pere Puigserver

Joshua A Bittker

Micah Maetani

Drew Adams

David Barnes-Seeman

Young-Hoon Ahn

Zoltan Maliga

Jun S Liu

Daniel B Graham

Jeffrey S Friedman

Lawrence MacPherson

Andre Fischer

Yun Kyung Kim

Hyman A Carrinski

Kfir Sharabi

Cigall Kadoch

Enrique Garcia-Rivera

Michael Durney

Roger Schilling

Nicole Maloof

Kazuo Nakai

Benjamin Stanton

Seung Bum Park

Robert A Stavenger

Brian G Gladstone

Abhinav Seth

Stephen D Liberles

Elizaveta Leshchiner

Kristopher M Depew

Paul Hergenrother

Provided herein are compounds useful for the treatment of various proliferative diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, and may be used in methods of treatment and/or prophylaxis of proliferative diseases, including cancer, and more specifically, pancreatic cancer.

Cyclopentaimidazolones for the treatment of cancer

Disclosed herein are compounds for the treatment of inflammatory bowel disease. Additionally, provided herein are compositions and methods for using these compounds and compositions in the treatment of inflammatory bowel disease in a subject.

Compositions and methods for treating inflammatory bowel disease

The present invention provides compounds, pharmaceutical compositions and methods for treating and/or preventing a metabolic condition, such as diabetes.

Selective inhibition of gluconeogenic activity

In one aspect, the present invention provides a method of inhibiting proliferation of a multiple myeloma cell, the method comprising contacting the cell with BRD9647, thereby inhibiting proliferation of the cell. In another aspect, the present invention provides a method of treating multiple myeloma in a pre-selected subject, the method comprising administering an effective amount of BRD9647 to the subject, wherein the subject is pre-selected by detecting a mutation in an AZIN1 polynucleotide or polypeptide relative to a reference in a biological sample obtained from the subject. In another aspect, the present invention provides a method of modulating benzoylation of an agent in a cell, the method comprising contacting the cell with BRD9647, thereby modulating benzoylation of an agent in the cell.

Compositions and methods for treating multiple myeloma

The present invention includes compound and methods that are useful in treating certain cancers, such as synovial sarcomas.

Compounds and methods for treating synovial sarcomas

The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)). 

Uses of salt-inducible kinase (SIK) inhibitors

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 invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: 

Compounds and methods for the treatment of isocitrate dehydrogenase related diseases

The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds. 

Deacetylase inhibitors and uses thereof

Certain embodiments disclosed herein are directed to a method of producing pancreatic cells or pancreatic cell precursors by exposing human embryonic stem cells to an effective amount of at least one compound listed in Table I to differentiate the human embryonic stem cells into the pancreatic cells or the pancreatic cell precursors. Kits and pancreatic cell lines produced using the methods are also described.

Compositions and methods for promoting the generation of PDX1+ pancreatic cells

Compounds including various oligomers of piperlongumine and/or piperlongumine analogues as well as certain piperlongumine analogues that exhibit improved toxicity to cancer cells are disclosed. Also provided are compositions that comprise the compounds, methods of making compositions comprising the compounds, methods of making the compounds, and the use of compounds in methods for treating cancer.

Compounds, compositions, and methods for cancer therapy

The present invention relates to the use of rosamine derivative compounds, as described herein, in detecting differentiated forms of a cell type of interest in a sample and in screening for compounds which inhibit differentiation of the cell type of interest. The candidate compound has the following structure: 

Combinatorial rosamine library to detect cell-state switching

Growing community of inventors

Boston, MA, United States of America

Stuart L Schreiber