Chemical & Engineering News Digital Edition

SYNTHONIX

IN THE LAB Chemists at work at Synthonix’ North Carolina facility.

went sour. Drug companies weren’t getting the results they had counted on from the expensive screening operations. At the same time, new computational techniques were allowing them to carry out some of the same screening with software rather than wet chemistry.

A MARKET GROWS,
BLOCK BY BLOCK
Pharmaceutical building-block business
attracts firms from ACROSS THE GLOBE
MICHAEL MCCOY, C&EN NORTHEAST NEWS BUREAU

WHEN DEREK LOWE, author of the In the Pipeline drug discovery blog, wrote a post about laboratory chemical suppliers last year, complaints from commiserating chemists soon flooded his comments section. Buying building-block chemicals for drug discovery, it seems, has become a little like shopping on eBay: Both bargains and pitfalls abound.

There was a time when medicinal chemists seeking to create a family of unique compounds would buy starting materials from one of a handful of U. S. catalog houses and create a suitable building block themselves. Today, dozens of synthesis labs across the globe vie to provide building blocks, and some U. S. firms have pulled back from the business.

Although chemists are happy with the convenience of off-the-shelf building blocks, they find themselves uneasy with the Wild West atmosphere of the global marketplace. U. S. companies, meanwhile, persist by offering quality, speed, and unique compounds that no one else has.

Pharmaceutical starting materials
have been around as long as laboratory
chemicals have been sold, and traditional
suppliers such as Sigma-Aldrich and Fisher
Scientific still play an important role. The
modern building-block business, though, is
an outgrowth of the combinatorial chem-
istry craze of the 1990s, when pharma-
ceutical companies used high-throughput
techniques to screen libraries of thousands
of compounds against drug targets.

MEDICINAL CHEMISTS retrenched, returning to their earlier practice of screening smaller, targeted collections of compounds, often based on computational leads or structural information gleaned from crystallographic or spectroscopic assessment of biological targets. Ryan Scientific and its screening-library partners were only too happy to provide chemists with building blocks to create targeted libraries.

One of these companies was Enamine, a Ukrainian firm founded in 1991, the year that the Soviet Union collapsed. At the time, high-throughput screening was just emerging, and creating libraries became a moneymaking endeavor for chemists who were struggling in the post-Soviet era. Compound suppliers such as ChemBridge, ChemDiv, Asinex, and Life Chemicals emerged from the region.

Enamine rose to be one of the leaders, amassing a screening library of 1. 7 million compounds—the world’s largest, it claims. As cofounder Aleksander Kostyuk recounts, business was good until about 2006, when Enamine’s sales of screening compounds started to decline. But when customers sought building blocks instead, Enamine jumped at the opportunity.

“We needed building blocks for our own production, so when we saw demand for building blocks, of course we started selling them as well,” Kostyuk explains.

Today Enamine offers more than 45,000 building blocks, all of which are in stock and ready to ship, Kostyuk says. Most are in Ukraine, but about 4,000 top sellers are stocked in the U. S. And with about 350 employees, Enamine is adding building blocks at a rate of 1,000 per month, with a focus on original, multifunctional compounds.

Recent cutbacks in R&D spending by pharmaceutical industry customers haven’t affected demand for building blocks, Kostyuk says. “Demand for building blocks is high and growing,” he claims.