Johns Hopkins University

Other

New York University

Jürgen Bosch

Timothy J Cardozo

Arturo Casadevall

Sondra Maureen Nemetski

Eric H Jung

Described herein are methods of treating or preventing a fungal infection by administering one or more compounds of the present invention to a subject. The methods of the present invention treat or prevent a fungal infection of, or a combination thereof, as examples. The compounds of the present invention may be administered to a subject with other agents such as antifungal agents.

Anti-fungal inhibitors

The present inventors discovered that the molecule pyridinylthiazolamine (PTA) specifically prevents the protein-protein interaction of hLC3 with hAtg3 in vitro and in cell based assays. The inventors have developed a novel class of PTA analogs which also prevents the protein-protein interaction of hLC3 with hAtg3 in vitro, and in cell based assays, and which can be used in prior to, or in combination with chemotherapeutic agents to treat proliferative diseases such as cancer.

Inhibitors of LC3/Atg3 interaction and their use in the treatment of cancer

Inhibitors of LC3/ATG3 interaction and their use in the treatment of cancer

In one aspect, the present invention relates to a method of identifying compounds useful in modifying the activity of Aldolase. The method includes providing a first model comprising Aldolase or residues of the amino acid sequence corresponding to SEQ ID NO: 1 said residues being at amino acid positions selected from the group consisting of 10-13, 26, 27, 29, 30, 31, 32, 33, 37, 39, 40, 41, 43, 44, 47, 48, 51, 52, 60, 63, 66, 79, 84, 85, 92, 93, 103, 106-109, 112-117, 138, 142, 146, 148, 151, 153, 179, 182, 183, 185, 186, 194, 196, 197, 198, 199, 208, 226-228, 231-269, 270, 272, 277-283, 285-289, 294, 295, 297-299, 301-304, 306-310, 312, 313, 316, 317, 319, 321, 323, 326, 330, 344, 345, and 347, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and/or fit in the first model, and identifying compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for modifying the activity of Aldolase. The present invention also discloses compounds and compositions which modify the activity of Aldolase, or a complex between Aldolase and TRAP. Methods of treating or preventing malaria, or an infection by apicomplexan organisms are also disclosed.

Small molecule malarial Aldolase-TRAP enhancers and glideosome inhibitors

Growing community of inventors

Pikesville, MD, United States of America

Jürgen Bosch