Vertex Pharmaceuticals, Inc.

Paul Lang

Michael P Mortimore

Julian M Golec

Thierry Hercend

Peter Weber

Anita Diu-Hercend

Karen Miller

Ronald Marcellus Knegtel

Andrew Miller

The present invention relates to methods for identifying compounds useful for regulating TNF-alpha levels and/or activity. The invention also relates to methods for decreasing TNF-alpha levels and/or activity. Compounds and compositions according to this invention are useful for treating TNF-mediated diseases. The invention also relates to kits comprising the compounds and compositions herein and a tool for measuring TNF-alpha activity and/or levels.

Regulation of TNF-alpha

The present invention relates to novel classes of compounds of formula I which are caspase and TNF-alpha inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase and TNF-alpha activity and consequently, can be advantageously used as agents against caspase-, interleukin-1-('IL-1'), apoptosis-, interferon-&#x3b3; inducing factor-(IGIF), interferon-&#x3b3;-('IFN-&#x3b3;'), or TNF-alpha mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to processes for preparing the compounds of this invention. This invention also relates to methods for inhibiting caspase and TNF-alpha activity and decreasing IGIF production and IFN-&#x3b3; production and methods for treating caspase-, interleukin-1, apoptosis-, and interferon-&#x3b3;-, and TNF-alpha mediated diseases using the compounds and compositions of this invention.

Caspase inhibitors and uses thereof

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Viuz en Sallaz, France

Paul Lang