New screening tech at Scripps spotlights diabetes drug candidates

The Scripps Research Institute has used a new drug screening platform to identify a drug which researchers believe has strong potential for treating diabetes.

Working with a technique dubbed autocrine selection, investigators are able to screen molecules in search of targets that can bind to and activate cellular receptors in order to achieve a sought-after drug effect.

In this latest study, published in Nature Communications, the Scripps team went after the GLP-1 receptor, which is already the target of a number of GLP-1 agonists. Scripps, though, wanted to activate the GLP-1 receptor's G protein pathway.

Hongkai Zhang focused on the GLP-1 agonist Extendin-4, whipping up a million peptides that could alter the end of the protein that activates the G protein and beta arrestin pathways.

"The idea was that at least one of these many variants would induce a change in the shape of the GLP-1 receptor that would activate the G-protein pathway without activating the beta arrestin pathway," Zhang said.

They then identified the one in a million that improved glucose tolerance at a radically reduced dose of Extendin-4, testing it on mice.

"P5's mechanisms of action turned out to be quite different from Exendin-4's, and we think that this finding could lead to new therapeutics," said Emmanuel Sturchler, a staff scientist in the McDonald laboratory and co-first author of the study.

- here's the release
- read the journal article

Suggested Articles

Astellas’ Xospata and Novartis’ Rydapt may help treat lung cancer that has grown resistant to EGFR inhibitors, researchers discovered.

Dutch scientists used stem cells from CF patients to demonstrate a technique that corrects a mutation in the gene CFTR without having to cut DNA.

A new map of the thymus gland could help researchers understand how T cells develop and inspire treatments for cancer and autoimmune disease.