Terra Sigillata

So say the American elder statesmen of natural products in the 2007 update of their periodic review of the subject to be published in the 23 March issue of the Journal of Natural Products. (Details are in this Reuters article with by Julie Steenhuysen). I will post more about the article when I get my hands on it, but it comes from NCI’s Dr David Newman and recently-retired Dr Gordon Cragg. Cragg had led the NCI Natural Products Branch, a position that Newman now holds.

Newman and colleague Gordon Cragg reviewed the origins of new drugs developed in the past quarter-century and found that despite the introduction of a host of high-tech drug discovery tools, natural products continue to be the inspiration for most new drugs.

Newman suggests that combinatorial synthetic chemistry approaches of the last decade or so have not been as fruitful as they were billed initially:

Their study indicates that a back-to-nature approach might yield better possibilities for companies looking for the next blockbuster drug.

Drug discovery hit a 24-year low in 2004, with just 25 unique compounds known as new chemical entities introduced that year, said David Newman, who runs the U.S.
National Cancer Institute’s natural products branch.

“Chemists started making libraries of hundreds of thousands to millions of compounds. But they were simple compounds,” he said in a telephone interview.

“Mother Nature doesn’t make simple compounds. Mother Nature wants compounds that fit into particular places.”

Interestingly, only two of the big US pharma houses maintain internal natural products drug discovery programs:

Newman links a dearth of new drug development at U.S. drug companies with the shift away from nature as a main source of drug compounds.

“Wyeth and Merck are the only two U.S. manufacturers of that size that still use natural products as one of their sources to look for drugs,” he said.

There are a few barriers to adopting natural products as drug sources, particularly when the plant, microorganism, or marine creature makes the active compound in vanishingly low quantities. (This point, incidentally, is why many herbal medicines are often ineffective: you can’t ingest enough of the plant material to have a biological effect.) However, approaches of semi-synthesis have proven useful (where an abundant intermediate is found in nature that can be manipulated to the final drug). More recently, some researchers have taken to cloning the biosynthetic genes whose encoded proteins are responsible for creating the natural compound.

I’ll have more to say on this topic once I read the article.

But the bottom line is that natural products represent medicine’s past, present and, hopefully, our future.