The identification of a new class of chemicals that bind to a previously unknown allosteric pocket ― a pocket outside the enzyme active site ― and inhibit the enzyme FPPS is reported online this week in Nature Chemical Biology. FPPS is an enzyme involved in lipid formation and is a potential target in multiple diseases, including cancer. This discovery could lead to the development of a new breed of antitumor therapeutics.

Bisphosphonates ― a class of FDA-approved drugs that are effective in the treatment of bone diseases such as osteoporosis ― are potent inhibitors of FPPS. It has been thought that bisphosphonates could be used as antitumor agents, but the high attraction of this class of chemicals to bone mineral makes them unsuitable for targeting most tumors. Using a combination of NMR spectroscopy and X-ray crystallography, Wolfgang Jahnke and colleagues identify a novel allosteric binding pocket that permits the inhibition of FPPS by new non-bisphosphonate types of chemicals. This finding opens up opportunities for further validation of FPPS as an anti-cancer target.