SHUTTERSTOCK
NEWS OF TH E WEEK
SEED TREATMENT QUESTIONED
cording to EPA. The two most widely used compounds for this purpose are imidacloprid and thiamethoxam. Pesticide manufacturer Syngenta, which makes thiamethoxam, says neonicotinoid seed treatments protect soybeans against early-season insects and provide “a faPESTICIDES: More effective insect vorable impact on cost and yield.” These treatments give controls than neonicotinoids are protection to soybean leaves for the plant’s first three available for soybeans, EPA says to four weeks. But, EPA points out, this isn’t when some pests targeted by the treatments, such as the soybean aphid, are the most active. REATING SEEDS with neonicotinoid insecti“Alternative insecticides applied as sprays are availcides provides little or no benefit for soybean able and effective” against soybean pests, EPA says in the production, says a new analysis by the Environanalysis, which was released on Oct. 16. Such alternamental Protection Agency. The agency is reviewing this tives are comparable in cost with neonicotinoids. controversial class of pesticides because of mounting Environmental advocacy groups are welcoming EPA’s concerns that these chemicals are linked with analysis. For years, these activists have urged EPA to a decline in bee populations. ban neonicotinoid pesticides because of their HN N Pesticide manufacturers are disputing the potential to harm bees. “It is abundantly clear report, saying EPA did not consider all available N N Cl that the costs of neonicotinoids outweigh NO2 information. Advocacy groups, meanwhile, say the benefits,” says Peter Jenkins, an attorthe analysis indicates that the use of neonicotiney with the Center for Food Safety. Jenkins is Imidacloprid noid pesticides on soybeans should cease. leading a lawsuit against EPA about the use of EPA’s analysis finds no difference in yield, neonicotinoids. O N N in most cases, when soybeans are treated with EPA is seeking public comments on its Cl analysis of the benefits of neonicotinoid seed neonicotinoids versus when they are not. N N S Today, about one-third of the soybeans treatments for soybeans. The review could CH3 NO2 planted in the U.S. each year are treated with lead EPA to halt or restrict certain uses of neoneonicotinoid pesticides before planting, acThiamethoxam nicotinoid pesticides.—BRITT ERICKSON
T
Seed treatments help protect leaves from pests during a soybean plant’s first three to four weeks.
TROUBLEMAKING ENZYME TRASHED DRUG DISCOVERY: Cancercausing pseudokinase directed to cellular garbage can
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NEW STUDY shows how pseudokinases, sig-
naling enzymes that cause cancers and blood diseases, can be inhibited effectively by small molecules, a feat many researchers in the field believed wasn’t possible. The work could lead to pseudokinasetargeted drugs that fight cancer and other conditions. Forty-eight pseudokinases account for 9% of the 520 kinases found in humans, notes Nathanael S. Gray of Dana-Farber Cancer Institute, in Boston, who
NAT. CHEM. BIOL.
A covalent inhibitor tags the cancer-related pseudokinase HER3 with the hydrophobic group adamantane, causing HER3 to interact with a chaperone. The chaperone delivers HER3 to the cellular garbage can, the proteasome, for disposal, impeding cancer-inducing HER3 dimerization.
CEN.ACS.ORG
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carried out the study with Dana-Farber colleague Pasi A Jänne, Craig M. Crews of Yale University, and coworkers (Nat. Chem. Biol. 2014, DOI: 10.1038/nchembio.1658). The team focused on the pseudokinase HER3, a target for ovarian, breast, and lung cancer. Pseudokinases are so called because they have kinase active sites but lack key residues needed for normal kinase activity. HER3’s principal activity is not phosphate transfer but rather forming cancer-inducing dimers with other proteins. Drug developers typically inhibit kinases by blocking adenosine triphosphate binding. But that strategy typically doesn’t work for pseudokinases. Now, the Dana-Farber/Yale group has identified a compound called TX2-121-1 that attaches covalently to HER3’s kinase active site. An adamantane hydrophobic group riding along with the inhibitor causes HER3 to interact with a chaperone that delivers HER3 to the proteasome, the cellular trash can. This blocks cancer-inducing HER3 dimerization in cells at the 1-µM level. “We are currently trying to get potency into the 100-nM range and exploring pharmacological properties, both needed before we move into any animal testing,” Gray says. Pseudokinase specialist Natalia Jura of the University of California, San Francisco, comments that the HER3elimination strategy is “a very promising beginning” and could be extended to blocking not only other pseudokinases but also conventional kinases that promote diseases by noncatalytic mechanisms.—STU BORMAN
OCTOBER 27, 2014
