IN THE LAB
Chemists at work
at Synthonix’ North
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.
But competition is also growing, par-
“It’s hard to compete dollar for dollar with China and India, but time
is equally important to researchers. Chemists are very impatient.”