7WWW.CEN-ONLINE.ORG AUGUST 9, 2010

NEWS OF THE WEEK

RESEARCHERS in California are reporting a small molecule that might help human blood stem cells propagate. The molecule, called SR1,

also targets a receptor not previously known to play a role in blood stem cell biology.

The intention of the new work is to increase the supply of these valuable human blood stem cells, which are required to replenish the blood and immune systems of leukemia patients and those experiencing the aftereffects of radiation therapy.

Blood stem cells, also known as he-matopoietic stem cells, have been trans-planted directly from bone marrow or umbilical cord blood donors into patients for decades. However, researchers have long wanted to find a way to cultivate the valuable cells in a lab prior to transplantation so that more patients could be treated from one donation. For instance, the stem cells in one umbilical cord blood donation aren’t enough to treat an adult, so the treatment is limited to children unless multiple suitable donors are found.

Researchers led by Peter G. Schultz at Scripps Re-search Institute and Michael P. Cooke at the Genomics Institute of the Novartis Research Foundation (GNF) screened a library of 100,000 heterocycles to find SR1, a purine derivative that, when added to a protein cock-tail, multiplies the number of blood stem cells 17 times

( Science, DOI: 10.1126/science.1191536). “It’s an important advance,” com-

ments Harvey F. Lodish, a stem cell researcher at Whitehead Institute for Biomedical Research. SR1 replaces two protein components in a cocktail previ-ously developed by Lodish and his for-mer postdoc Chengcheng Zhang, now a stem cell biologist at the University of

Texas Southwestern Medical Center. That cocktail, which propagates blood stem cells by an amount

similar to the SR1-containing mix-ture, will soon go into clinical trials at

Singapore General Hospital. Using the small molecule instead

of proteins could simplify proce-dures to propagate blood stem

cells should they reach a clinical setting, comments

Christopher Y. Park, who specializes in stem cells and

cancer at Memorial Sloan-Kettering Cancer Center.

The Scripps and GNF research-ers report that SR1 works by antag-

onizing the aryl hydrocarbon recep-tor, a previously unknown player in blood stem cell biology. “This opens up the possibility of further under-standing how human hematopoietic stem cells are regulated, which then allows one to try to modulate human hematopoietic stem cell activity for clinical benefit in other ways,” com-ments Hal E. Broxmeyer, a stem cell researcher at Indiana University School of Medicine. —SARAH EVERTS

PROPAGATION AID As shown in these optical microscopy images, SR1 helps blood stem cells proliferate (various colors, bottom) instead of differentiating into blood cells (purple, top) after five days. Images are at 40× magnification.

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MULTIPLIER MEDICINAL CHEMISTRY: Small

molecule spurs the proliferation of blood stem cells

Speculation is mounting that the French pharmaceutical giant Sanofi-Aventis is pursuing the acquisition of Genzyme. According to media reports, Sanofi has sent a letter to the Massachusetts-based biotech firm offering to buy it for $69.00 per share, or roughly $18.4 billion.

The letter kicks off what observers ex-pect to be protracted negotiations between the firms. Most analysts think a deal will eventually be sealed for a price per share in the mid-$70s, or around $20 billion.

Genzyme makes for an attractive target. Despite a healthy portfolio of drugs for rare diseases, the firm has seen its value sink because of manufacturing problems at its

site in Allston, Mass. The deficiencies have caused shortages of two products, Fabra-zyme for Fabry disease and Cerezyme for Gaucher disease, and led the U.S. govern-ment to fine the company $175 million (C&EN, May 31, page 33).

Some analysts think Genzyme is in no rush to be acquired during this troubled period. “Our sense is that Genzyme’s management is not overly interested in selling at this point and would rather wait until they fix the manufacturing problems in 2011,” Citigroup analyst Mark Dainty told investors in a recent report. But Cowen & Co. analyst Philip Nadeau notes that Genzyme’s frustrated share-

holders and activist management board could push the firm to accept the offer.

An acquisition would cap a buying spree by Sanofi, which in the past year has increased its focus on external op-portunities while cutting back on its own R&D. Since June, Sanofi has signed development deals with Metabolex, for a type 2 diabetes drug; Regulus, for microRNA-based drugs; Ascenta Thera-peutics, for small molecules that block protein-protein interactions; and Vivalis, for monoclonal antibodies that fight infec-tious disease. It also acquired TargeGen, which develops small-molecule kinase inhibitors.—LISA JARVIS

PHARMACEUTICALS Sanofi-Aventis sets its sights on biotech firm Genzyme

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SR1