Science Concentrates DRUG DISCOVERY
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Circadian clock activators kill cancer cells One of the compounds also reduces brain cancer growth in mice Women who work night shifts have substantially higher risks of breast, digestive system, and skin cancers, a recent study found. The findings reinforce a connection researchers have observed between cancer and the circadian clock, a biological system that controls the daily schedule of physiological processes. Now, in findings that could lead to a new class of cancer drugs, researchers have uncovered a key molecular link between circadian rhythm and cancer. The nuclear hormone receptors REV-ERBα and REV-ERBβ are essential components of the body’s circadian clock. Gabriele Sulli and Satchidananda Panda at Salk Institute for Biological Studies and coworkers show that when each of two small organic molecules, SR9009 and SR9011, turn on the receptors in cell culture, the interactions kill leukemia, melanoma, breast cancer, colon cancer, and brain cancer cells, as well as dormant premalignant cancer cells (Nature 2018, DOI: 10.1038/nature25170). SR9009 also reduced the growth of glioblastoma, a form of brain cancer, and lengthened survival time in mice with glioblastoma tumors. It worked about as
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ty, designed and synthesized effectively as temozolomide, the current SR9009 and SR9011 to activate standard treatment for glioblastoma, REV-ERB receptors (Nature 2012, but it did so without any apparent side DOI: 10.1038/nature11030). They effects. Temozolomide often causes hair showed that the compounds had metaloss, gastrointestinal upset, and nervous bolic effects—obese mice treated with system problems, among other side efthe compounds lost weight. Based on the fects. SR9009 and SR9011 both pass the previously observed associations between blood-brain barrier, enabling them to the circadian clock and cancer, Sulli, reach the brain, but they are not orally Panda, and coworkers speculated that the available, so researchers had to inject compounds might affect cancer them into the animals. Cl cell viability as well. Panda notes The data suggest that circadianthat patents for the compounds are clock-targeted agents could treat a owned by Scripps and that “there wide range of cancers with few side is no immediate commercialization effects, the researchers say. But they plan from Salk.” point out that further safety testN “I’m happy to see this type ing and trials in people are of anticancer activity, alnecessary. S The Salk team N O2N O though I’m sorry that we didn’t find it first,” Burris found that the two O says. “The true test will compounds kill cancer cells by SR9009 be getting SR9009 and inhibiting lipid production and SR9011 into human trials autophagy, a process in which cells to see if they are beneficial. I’m curious degrade unwanted cellular components. to see how they will work with other Cancer cells need both metabolic processchemotherapeutic agents because canes to grow and reproduce. cer is often treated with multiple drugs In 2012, a group led by Thomas P. Burat once to avoid the development of ris, then at Scripps Research Institute resistance.”—STU BORMAN Florida and now at St. Louis Universi-
CATALYSIS
Activating C–H bonds with isolated atoms Sprinkling individual platinum atoms across a copper surface yields an energy-efficient and durable bimetallic catalyst that effectively mediates reactions involving C–H bond activation, according to a study (Nat. Chem. 2018, DOI: 10.1038/ nchem.2915). Breaking C–H bonds is the first step in converting relatively inert compounds such as methane and other alkanes to more valuable fuels and chemicals. Industrial processes for carrying out this type of chemistry are well developed. Many manufacturers rely on steam cracking, for example, to convert ethane to
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C&EN | CEN.ACS.ORG | JANUARY 15, 2018
ethylene. But that process is energy intensive. Catalysts can mediate C–H-activation chemistry and reduce the required energy input, but they have shortcomings. Platinum, for example, can dramatically reduce the temperature for C–H activation, but it is expensive. Nickel, which is relatively inexpensive, also works as a C–H activation catalyst, but both it and platinum are prone to coking, a process that generates a film of carbon (coke) that gunks up the catalyst surface and blocks reagents’ access to catalytic sites. Copper resists coking but it is a weak catalyst. So in a follow-up to earlier work with
single-atom catalysts, E. Charles H. Sykes and Maria Flytzani-Stephanopoulos of Tufts University and Michail Stamatakis of University College London conducted catalytic reaction tests on methyl groups, methane, and butane using copper surfaces dotted with isolated platinum atoms. The team found that compared with pure copper, the bimetallic catalysts avoid coking and lower the C–H activation temperature by 100 °C or more depending on the reaction. The bimetallic catalysts address the platinum cost problem by using the metal as sparingly as possible on the copper surfaces.—MITCH JACOBY
