Georgia Tech Research Corporation

Emory University

Jonathan D Glass

James C Powers

Zhaozhao Li

Asli Ovat

A novel class of peptide &#x3b1;-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA-AA-CO&#x2014;NH&#x2014;(CH)&#x2014;R. Processes for the synthesis of peptidyl &#x3b1;-ketoamide derivatives. Compositions and methods for inhibiting cysteine proteases, inhibiting calpains, and treating disease caused by cysteine proteases and calpains are provided.

Heterocyclic peptide ketoamides

Methods for treatment and/or prevention of nerve degeneration in mammals using aza-peptide epoxide caspase inhibitors are provided. Aspects of the present disclosure include aza-peptide epoxide compositions to treat or prevent diseases, for example stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, neuropathies, Huntington's disease, dentatorubropallidoluysian atrophy, spinocerebellar atrophies, spinal bulbar muscular atrophy, diabetes, amyotrophic lateral sclerosis and other motor neuron diseases. The disclosed methods can be used in combination with calpain inhibitors to treat disease or pathological conditions related to the activity of caspases and calpain associated with a specific disease or condition. Such treatable conditions include stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, neuropathies, Huntington's disease, dentatorubropallidoluysian atrophy, spinocerebellar atrophies, spinal bulbar muscular atrophy, nerve degeneration associated with diabetes, amyotrophic lateral sclerosis and other motor neuron diseases, nerve degeneration secondary to primary demyelinating disorders, among others.

Aza-peptide epoxides

Compositions and methods for treating neural pathologies are provided. In particular, compositions and methods for treating neural pathologies including axonal degeneration are provided. The compositions include peptide &#x3b1;-ketomides optionally in combination with a second therapeutic agent. Another aspect of the invention provides compositions and methods for treating hyperproliferative disorders. Exemplary compositions for treating hyperproliferative disorders include an anti-proliferative agent such as paclitaxel, in combination with a calpain inhibitor such as AK295.

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Atlanta, GA, United States of America

Jonathan D Glass