Whitehead Institute for Biomedical Research

Massachusetts Institute of Technology

The Broad Institute, Inc.

The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

Luke Whitesell

Susan Lindquist

Stephen L Buchwald

Benito Munoz

Sivaraman Dandapani

Jean-Baptiste Langlois

Benjamin Vincent

Willmen Youngsaye

Ralph Mazitschek

Partha Pratim Nag

Tan A Ince

Jun Pu

Amal Ting

Raja Srinivas

Bruce Tidor

Sandro Santagata

Barbara J Morgan

Catherine McLellan

The present invention provides novel compounds (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrate, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits comprising the inventive Compounds, or compositions thereof, for treating and/or preventing a fungal or protozoan infection, inhibiting the activity of a fungal or protozoan enzyme, killing a fungus or protozoan, or inhibiting the growth of a fungus or protozoan. The fungus may be aspecies,species, or other pathogenic fungal species. The compounds of the invention may inhibit the activity of fungal or protozoan mitochondrial phosphate carrier protein.

Thiohydantoin derivatives and uses thereof

The present invention provides novel compounds (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits comprising the inventive compounds, or compositions thereof, for treating and/or preventing a fungal or protozoan infection, inhibiting the activity of a fungal or protozoan enzyme, killing a fungus or protozoon, or inhibiting the growth of a fungus or protozoon. The fungus may be aspecies,species, or other pathogenic fungal species. The compounds of the invention may inhibit the activity of fungal or protozoan cytochrome b and/or fungal or protozoan Hsp90. The present invention also provides synthetic methods of the inventive compounds. 

Indazole derivatives and uses thereof

In some aspects, the invention relates to Heat Shock Protein-1 (HSF1) gene and HSF1 gene products. In some aspects, the invention provides methods of tumor diagnosis, prognosis, treatment-specific prediction, or treatment selection, the methods comprising assessing the level of HSF1 expression or HSF1 activation in a sample obtained from the tumor. In some aspects, the invention relates to the discovery that increased HSF1 expression and increased HSF1 activation correlate with poor outcome in cancer, e.g., breast cancer.

HSF1 as a marker in tumor prognosis and treatment

The present invention provides compounds of Formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting fungal or parasitic growth. The compounds are useful as inhibitors of glycosylphosphatidylinositol (GPI)-anchor biosynthesis, in particular, as inhibitors of fungal Gwt1 activity. The present invention further provides methods of using the compounds described herein for treating fungal or parasitic infections. The compounds can also be used as biological probes to study the effects of inhibiting Gwt1 activity.

Compounds for treating infectious diseases

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Somerville, MA, United States of America

Luke Whitesell