Massachusetts Institute of Technology

The Broad Institute, Inc.

Whitehead Institute for Biomedical Research

Bruce Tidor

Douglas A Lauffenburger

Casim A Sarkar

Benito Munoz

Stephen L Buchwald

Susan Lindquist

Sivaraman Dandapani

Partha Pratim Nag

Jean-Baptiste Langlois

Benjamin Vincent

Amal Ting

Raja Srinivas

Willmen Youngsaye

Luke Whitesell

Sara E Dempster

Barbara J Morgan

Lee-Peng Lee

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

The present invention relates to granulocyte colony stimulating factor ('G-CSF') analog polypeptide compositions, related nucleic acids, expression constructs, host cells, and processes for recombinant production of the present G-CSF analogs. The concept detailed herein involves novel mutants of G-CSF, using single substitutions to amino acids, which were rationally chosen to affect the cellular trafficking of G-CSF and/or G-CSFR. In addition, pharmaceutical compositions, and methods of use are provided.

Methods of using G-CSF analog compositions

G-CSF analog compositions and methods

The present computer-implemented process involves a methodology for determining properties of ligands which in turn can be used for designing ligands for binding with protein or other molecular targets, for example, HIV targets. The methodology defines the electrostatic complement for a given target site and geometry. The electrostatic complement may be used with steric complement for the target site to discover ligands through explicit construction and through the design or bias of combinatorial libraries. The definition of an electrostatic complement, i.e., the optimal tradeoff between unfavorable desolvation energy and favorable interactions in the complex, has been discovered to be useful in ligand design. This methodology essentially inverts the design problem by defining the properties of the optimal ligand based on physical principles. These properties provide a clear and precise standard to which trial ligands may be compared and can be used as a template in the modification of existing ligands and the de novo construction of new ligands. The electrostatic complement for a given target site is defined by a charge distribution which minimizes the electrostatic contribution to binding at the binding sites on the molecule in a given solvent. One way to represent the charge distribution in a computer system is as a set of multipoles. By identifying molecules having point charges that match this optimum charge distribution, the determined charge distribution may be used to identify ligands, to design drugs, and to design combinatorial libraries.

Computer system and process for identifying a charge distribution which minimizes electrostatic contribution to binding at binding between a ligand and a molecule in a solvent and uses thereof

Growing community of inventors

Lexington, MA, United States of America

Bruce Tidor