Emory University

Harvard College

University of California

Children's Healthcare of Atlanta, Inc.

Haian Fu

R John Collier

Yuhong Du

David S Eisenberg

Keqiang Ye

Raymond J Dingledine

Seunghyon Choe

Shane C Masters

Zhi Ren

Andras Rab

Xun Yang

Candela Manfredi

Eric Sorscher

Jeong Hong

This disclosure relates to compounds that are cystic fibrosis transmembrane conductance regulator (CFTR) modulators and pharmaceutical compositions containing the same. In certain embodiments, this disclosure relates to methods of managing a CFTR related disease or condition or respiratory distress comprising administering an effective amount of a CFTR modulator disclosed herein to a subject in need thereof.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pharmaceutical compositions, and uses thereof

This disclosure relates to asparagine endopeptidase inhibitors for managing cancer and compositions related thereto. In certain embodiments, the asparagine endopeptidase inhibitors are substituted 3,7-dihydropurine-2,6-dione derivatives useful for treating or preventing metastasis, tumor growth, and/or cancer. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising an asparagine endopeptidase inhibitor and a pharmaceutically acceptable excipient. In certain embodiments, the disclosure relates to methods of treating a cancer comprising administering an effective amount of pharmaceutical composition a asparagine endopeptidase inhibitor disclosed herein to a subject in need thereof.

Asparagine endopeptidase (AEP) inhibitors for managing cancer and compositions related thereto

Methods are provided for enhancing the death of a neaplastic cell comprising the administration of a therapeutically effective concentration of a 14-3-3 antagonist and at least one antineoplastic therapeutic agent. The methods of the invention find use in improving the clinical outcome of a mammal having a neoplastic disorder and comprises administration to a mammal in need thereof at least one antineoplastic therapeutic agent in combination with a 14-3-3 antagonist. Further provided are pharmaceutical compositions having a therapeutically effective amount of a 14-3-3 antagonist and an antineoplastic therapeutic agent. Also provided are methods for identifying agents that selectively inhibit an interaction between a 14-3-3 polypeptide and a 14-3-3 ligand.

14-3-3 binding molecules as sensitizers for anticancer therapies

The invention features a polypeptide consisting of amino acids 379-535 of diphtheria toxin, and portions thereof. This region, shown by X-ray crystallographic analysis to comprise the receptor binding domain of diphtheria toxin, is used as an immunogen and clinical therapeutic against diphtheria.

Diphtheria toxin receptor-binding region

The invention provides a cytotoxicity-based genetic selection (TOXSEL) method and related testing kit for the identification and positive selection of molecules or mutations that are capable of disrupting a specific protein--protein interaction. The invention enables positive selection of molecules disruptive of specific protein--protein interactions by virtue of the presence in the TOXSEL system of a toxin reporter gene. A disrupted protein--protein interaction precludes expression of the toxin reporter gene and, consequently, allows survival of the host cell. TOXSEL technology enables large-scale screening for drugs or small molecules capable of disrupting specific protein--protein interactions critical in processes such as cellular signalling, carcinogenesis, etc. The positive selection of molecules or mutations capable of interfering with specific protein--protein interactions permits the identification of amino acid residues or motifs critical in the protein--protein interactions and permits the design of drugs for therapeutic or diagnostic applications.

Cytotoxicity-based genetic selection system (TOXSEL)

Growing community of inventors

Decatur, GA, United States of America

Haian Fu