CytRx Corporation, a biopharmaceutical company engaged in the development and commercialisation of human therapeutics, said scientists at its San Diego laboratory have discovered a novel series of compounds that amplify the natural cellular chaperone response to toxic misfolded proteins in cell culture, providing potential pipeline leads for next generation drug candidates in a number of disease indications, including cancer, cardiovascular disease, diabetes and neurodegenerative diseases.
Shi Chung Ng, Ph.D., senior vice president research and development, CytRx, said, "We are excited by the rapid progress made in our laboratory in the short time since September 2007 when we started operations in our San Diego facility. Before this discovery could result in any clinical candidates, we plan to file a patent application for these compounds, followed by submission of our study results for publication in a peer-reviewed journal, while we continue the process of compound characterization and lead optimization."
During conditions that are stressful to cells, such as during certain disease states, proteins can fold into inappropriate, toxic shapes. These misfolded proteins are recognized to be undesirable by a group of proteins called molecular chaperones, and consequently are either re-folded or directed to protein degradation machinery in the cell. Small molecule amplifiers of the chaperone response, as CytRx's clinical candidates arimoclomol and iroxanadine are believed to be, have shown promising results in animal models of neurological impairment and diabetic complications.
Using sophisticated, image-based high-content screening technologies developed at the company's San Diego laboratory, CytRx scientists have identified a novel series of compounds that by themselves have shown no effect on normal, unstressed cells culture, but can amplify the chaperone response in the presence of stress that leads to the generation of toxic misfolded proteins. As expected due to the known cytoprotective properties of molecular chaperones, these compounds also significantly protected cultured cells exposed to stress such as heat shock or oxygen and glucose deprivation, the latter of which is a cell-based model for stroke.