March 19, 2014

Small molecule protects kidney filter

A compound identified at Vanderbilt has therapeutic potential in protecting the kidney filter barrier.

A compound discovered at Vanderbilt University Medical Center has shed light on the nature of proteinuric kidney disease, damage to the kidney filter barrier caused by chronic conditions including obesity, hypertension and diabetes.

Reporting in the December 2013 issue of the Journal of Clinical Investigation, researchers led by a group at Harvard Medical School identified the calcium-permeable channel TRPC5 as a mediator of filtration barrier injury, and found that blocking the channel with a small molecule can protect the kidney filter.

The inhibitory compound, ML204, was identified in 2011 using a cell-based high throughput fluorescence assay by a multi-center team co-led by Vanderbilt’s Corey Hopkins, Ph.D., and Craig Lindsley, Ph.D., who also participated in the current study.

A leaky filter barrier is a risk factor for cardiovascular disease, kidney failure and death. The use of ML204 in this study highlights the importance of highly selective small molecules to probe the physiological role of targets for potential new treatments, the researchers said.

The Vanderbilt contribution to the study was made possible by a National Institute of Health/Molecular Libraries Probe Production Centers Network grant, MH084659.

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