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NEWS OF THE WEEKRoche hopesto expand itsdiagnosticinstrumentationbusiness byacquiring Illumina.ROCHEROCHE BIDS TOBUY ILLUMINADIAGNOSTICS: Acquisition wouldcreate a leading manufacturer ofgene-sequencing instrumentsROCHE HAS MADE a hostile move to acquireIllumina for $5.7 billion in cash. The Swissdrugmaker says it made the bid after Illumina ,a provider of gene-sequencing technology, refused toparticipate in “substantive discussions” about a friendlyacquisition.“We remain willing to engage in a constructivedialogue with Illumina to jointly develop an optimalstrategy for maximizing the value of our combinedbusiness,” Roche CEO Severin Schwan said last weekwhen announcing Roche’s offer to buy shares fromstockholders without Illumina’s blessing. To allow timeto review the offer, Illumina’s board has responded byadopting a shareholder rights plan, “designed to detercoercive or otherwise unfair takeover tactics.”Illumina dominates the market for next-generationsequencing, followed by Life Technologies and RocheDiagnostics , according to the research firm Frost & Sullivan.After restructuring and cutting 200 jobs late lastyear, Illumina anticipates reporting 2011 revenues ofnearly $1.1 billion.Roche Diagnostics wants to combine Illuminawith its Applied Science unit and move the business’sheadquarters from Germany to Illumina’s home in SanDiego. The acquisition would add to Roche’s position ingenetic and genome sequencing and microarrays. At thesame time, Roche envisions that it could help acceleratethe transition of DNA sequencing into clinical and routinediagnostic applications.“The proposed acquisition will strengthen Roche’scurrent offering in the life science market by providingcomplementary solutions to our current portfolio,”says Daniel O’Day, chief operating officer of RocheDiagnostics. The combined offering, he adds, would“help enable the discovery of complex new biomarkers,improving drug discovery and the selection of patientsmost likely to respond to a targeted treatment.”Roche’s $44.50-per-share offer is a 64% premiumover Illumina’s stock price on Dec. 21, 2011, the daybefore rumors about a potential deal began. Since then,the company’s stock price has risen about 40%.Although Roche’s bid is a bit high, “a premium is justified,”Mizuho Securities USA stock analyst Peter Lawsontold clients in a report. He bases his assessment onIllumina’s market dominance and its potential synergieswith Roche’s life science, diagnostic, and pharmaceuticalbusinesses, as well as prospects for “long-termsustainable growth.” —ANN THAYERNATUREStructure ofcytochromeP450 17A1, withprostate cancerdrug abiraterone(center, mostlyblack) bound to theenzyme’s heme iron(sphere).PROSTATE CANCERTARGET ANALYZEDMOLECULAR STRUCTURE: Detailed viewof cancer-related cytochrome P450could aid drug designTO UNDERSTAND BETTER how two new anticanceragents work, researchers have obtainedthe first X-ray structures of a key cytochromeP450 enzyme to which they bind. Understanding howthe drugs inhibit the enzyme could aid the designof more effective medications forprostate and breast cancer with fewerside effects.Cytochrome P450 17A1 (CYP17A1)is found in cell membranes in the humanreproductive tract and adrenal gland,where it catalyzes sequential hydroxylaseand lyase reactions in the biosynthesis oftestosterone and other sex hormones. Theapproved Janssen Biotech drug abiraterone( Zytiga ) and the Tokai Pharmaceuticalsagent TOK-001 (Galeterone), which is inclinical trials, are prostate cancer treatmentsthat work by inhibiting both the enzyme’s lyaseactivity, accounting for most of their efficacy, and itshydroxylase activity, which causes side effects.Emily E. Scott , an associate professor of medicinalchemistry, and Natasha M. DeVore at the Universityof Kansas have obtained X-ray structures by gettingCYP17A1 to crystallize with each of these drugs bound( Nature, DOI: 10.1038/nature10743 ).The structures reveal that the drugs bind to theenzyme in a manner far different from what scientistsexpected. Modeling studies had suggested the drugswould orient parallel to the plane of the enzyme’sactive-site heme group; instead, the drugs are nearlyperpendicular to it.Other P450 enzymes have been analyzed structurally,says cytochrome P450 specialist Paul Ortiz deMontellano of the University of California, San Francisco.But the new structures are “particularly important”in the search for prostate and breast cancer drugswith fewer side effects. For instance, they could leadto medications highly selective for CYP17A1, one of 57similar P450 enzymes found in humans.Scott says her group is collaborating with that ofUniversity of Kansas synthetic chemist Jeffrey Aubé “todesign new compounds we hope will be more selectivedrugs”—by inhibiting the enzyme’s lyase but not its hydroxylaseactivity, for example. — STU BORMANReprinted from C&EN, Jan. 30, 2012 (both)WWW.CEN-ONLINE.ORG 4 MARCH 2012