New York University

David Ron

Heather Harding

Timothy J Cardozo

Hong Wang

Yuhong Zhang

Marcella Calfon

Céline Jousse

The present invention relates to a method of identifying compounds useful in inhibiting protein kinase-like endoplasmic reticulum protein kinase (PERK). The method comprises providing a first model comprising PERK active domains, where the said active domains are selected from the group consisting of the peptide spanning from amino acid residue Asp144 to amino acid residue Ser191 of SEQ ID NO: 1 and a peptide comprising the amino acid residue at position 7 of SEQ ID NO: 1, 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 the compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for inhibiting PERK. The present invention further relates to compounds that can be used for inhibition of PERK, for example human PERK, and methods related to treatment of PERK-mediated diseases.

Method of treating cancer by inhibition of protein kinase-like endoplasmic reticulum protein kinase

The present invention relates to a method of screening a compound for potential effectiveness in treating or preventing a mammalian disease mediated by plasma cells or a mammalian disease caused by virus infection of mammalian cells. Compounds are tested for their ability to inhibit IRE1-mediated processing of untranslatable XBP-1 mRNA into translatable XBP-1 mRNA. Drugs that are useful in treating or preventing a mammalian disease mediated by plasma cells and a method for detecting XBP-1 activity in living cells are also described.

Method of screening test substances for treating or preventing a disease mediated by plasma cells

The invention is directed to methods for identifying test substances useful for the prevention or treatment of diseases involving an oxidative stress. The methods involve screening assays, including high throughput screening techniques, in which the test substances are tested for their ability to promote resistance to oxidative stress by activating one or more points of the integrated stress response pathway, while not causing stress.

Method of identifying substances useful for promoting resistance to cell stress

The invention is directed to methods and reagents for identifying test substances useful for the prevention or treatment of diseases involving an oxidative stress. The methods involve screening assays, including high throughput screening techniques, in which the test substances are tested for their ability to promote resistance to oxidative stress by inhibiting the activity of GADD34L, and thereby inhibiting the dephosphorylation of eIF2&#x3b1;, while not causing stress.

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New York, NY, United States of America

David Ron