Stage fright: don't get over it, get used to it

Many can feel empathy with the situation Banerjee describes: facing “a room full of scientists, who for whatever reason, did not look very happy that Read more

Beyond birthmarks and beta blockers, to cancer prevention

Ahead of this week’s Morningside Center conference on repurposing drugs, we wanted to highlight a recent paper in NPJ Precision Oncology by dermatologist Jack Arbiser. It may represent a new chapter in the story of the beta-blocker propranolol. Several years ago, doctors in France accidentally discovered that propranolol is effective against hemangiomas: bright red birthmarks made of extra blood vessels, which appear in infancy. Hemangiomas often don’t need treatment and regress naturally, but some can lead Read more

Drying up the HIV reservoir

Wnt is one of those funky developmental signaling pathways that gets re-used over and over again, whether it’s in the early embryo, the brain or the Read more

phospholipids

Biochemists grab slippery target: LRH-1

To fight fat, scientists had to figure out how to pin down a greasy, slippery target. Researchers at Emory University and Baylor College of Medicine have identified compounds that potently activate LRH-1, a liver protein that regulates the metabolism of fat and sugar. These compounds have potential for treating diabetes, fatty liver disease and inflammatory bowel disease.

Their findings were recently published online in Journal of Medicinal Chemistry.

LRH-1 is thought to sense metabolic state by binding a still-undetermined group of greasy molecules: lipids or phospholipids. It is a nuclear receptor, a type of protein that turns on genes in response to hormones or vitamins. The challenge scientists faced was in designing drugs that fit into the same slot occupied by the lipids.

“Phospholipids are typically big, greasy molecules that are hard to deliver as drugs, since they are quickly taken apart by the digestive system,” says Eric Ortlund, PhD, associate professor of biochemistry at Emory University School of Medicine. “We designed some substitutes that don’t fall apart, and they’re highly effective – 100 times more potent that what’s been found already.”

Previous attempts to design drugs that target LRH-1 ran into trouble because of the grease. Two very similar molecules might bind LRH-1 in opposite orientations. Ortlund’s lab worked with Emory chemist Nathan Jui, PhD and his colleagues to synthesize a large number of compounds, designing a “hook” that kept them in place. Based on previous structural studies, the hook could stop potential drugs from rotating around unpredictably. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment