The Broad Institute, Inc.

The General Hospital Corporation

Harvard College

Instituto Carlos Slim De La Salud, A.c.

New York University

The Brigham and Women's Hospital, Inc.

The General Hospital Corporation D/b/a Massachusetts General Hospital

Bridget K Wagner

Edward Holson

Florence Fevrier Wagner

Stephen J Haggarty

Michael C Lewis

Yan-Ling Zhang

Sean M Burns

Amedeo Vetere

Tracey Lynn Petryshen

Morten Lundh

Stuart L Schreiber

Young-Tae Chang

Amit Choudhary

Jeremy Duvall

Basudeb Maji

Miseon Lee

Young-Hoon Ahn

Paul A Clemons

Debasish Manna

Yun Kyung Kim

Hyman A Carrinski

Danny Hung-Chieh Chou

Steven Haggarty

Michael Lewis

Disclosed herein are methods for inducing insulin secretion in a glucose-dependent manner and compounds for use in these methods.

Compounds and methods for regulating insulin secretion

The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to β-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to β-cells that stabilize and activate CRISPR effector proteins comprising at least one destabilization domain, to enable CRISPR-based genome editing and transcriptional activation or repression in β-cells.

Targeted delivery to beta cells

Disclosed herein are methods for inducing insulin secretion in a glucose-dependent manner and compounds for use in these methods. The compounds may have the structure of formula I(a): wherein the substituents are as described in the description;or a pharmaceutically acceptable form thereof.

The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X, X, X, X, X, W, W, W, and Ware as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting &#x3b2;-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals.

Inhibitors of histone deacetylase

The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X, X, X, X, X, W, W, W, and Ware as described. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting &#x3b2;-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals. 

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

The invention relates to a compound of Formula I: 

Compounds and methods for treating autoimmune diseases

Growing community of inventors

Cambridge, MA, United States of America

Bridget K Wagner