Binding the intractable

Metabasis Therapeutics Inc. believes it is one of the first companies to develop a compound that selectively stimulates AMP-activated protein kinase, a metabolic disease target that it says has stymied researchers for about 20 years. Last week, Merck & Co. Inc. and MBRX partnered to develop small molecules that activate AMPK to treat Type II diabetes, hyperlipidemia and obesity.

AMPK plays roles in diabetes, cholesterol synthesis, fat synthesis and energy metabolism. But no one else has been able to find druggable modulators of the kinase, according to Mark Erion, executive vice president of R&D at MBRX (San Diego, Calif.). The company credits its NuMimetic technology for finding molecules that bind to AMPK. NuMimetic is designed to identify molecules that bind specifically to regulatory sites, called nucleotide binding sites, residing on enzymes involved in metabolic pathways. ...