Google Glass Might One Day Diagnose And Track Diseases Like HIV
Feb28

Google Glass Might One Day Diagnose And Track Diseases Like HIV

When Google began releasing its new head-mounted computer to beta testers last year, technology enthusiasts were pumped. After all, the futuristic device, called Glass, might one day enable people to answer email hands-free or view driving directions projected onto the road in front of them. Others, though, have complained that Google Glass is a cool piece of tech that hasn’t yet justified its existence. (Still others have complained that Glass is creepy, but that’s a story for another day.) Slowly but surely, though, beta testers in Google’s Explorers program have been making a case for the sophisticated eyewear by demonstrating its unique—sometimes scientific--capabilities. Physics teacher Andrew Vanden Heuvel famously shared his visit to the Large Hadron Collider, in Switzerland, with his students via Glass. Ohio surgeon Christopher Kaeding gave medical students a live, bird’s eye view of a knee operation he conducted while wearing the device. And now, a research team led by Aydogan Ozcan of the University of California, Los Angeles, is using Google Glass to help diagnose and track disease. The engineers designed an app for the wearable computer that images and reads rapid diagnostic tests such as pregnancy pee sticks. It also links the results to a scannable QR code, stores them, and tags them geographically. “The new technology could enhance the tracking of dangerous diseases and improve response time in disaster-relief areas or quarantine zones where conventional medical tools are not available or feasible,” Ozcan says. Among the first to be selected by Google as Explorers, Ozcan and his team demonstrated the capabilities of their new app by using it to read a few types of home HIV and prostate cancer tests—ones that require an oral swab or a drop of blood to work. They recently published their efforts in ACS Nano (2014, DOI: 10.1021/nn500614k). True, it doesn’t take much to read one of these tests—either lines appear or they don’t in the case of the HIV tests. But the app could save time for clinicians who routinely have to read a multitude of different types of sticks and remember which symbols and lines signify a positive or negative result, Ozcan points out. After a single calibration run, the online tool recognizes a particular test stick and can even assign a biomarker concentration to the lines that appear. These rapid diagnostic tests typically use nanoparticles to create these lines (which is why Ozcan’s study appears in ACS Nano). Coated with an antibody, the particles recognize a specific biomarker in blood, urine, or saliva samples and bind to it. As the particle-biomarker complex flows down the test stick, rows of a different type of antibody already...

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Exploring Rational Drug Design
Feb17

Exploring Rational Drug Design

Medicinal chemists strive to optimize molecules that fit snugly into their proposed targets. But in the quest for potency, we often overlook the local physics that govern drugs’ binding to these receptors. What if we could rationally predict which drugs bind well to their targets? A new review, currently out on J. Med. Chem. ASAP, lays out all the computational backing behind this venture. Three computational chemists (David Huggins, Woody Sherman, and Bruce Tidor) break down five binding events from the point-of-view of the drug target: Shape Complementarity, Electrostatics, Protein Flexibility, Explicit Water Displacement, and Allosteric Modulation….whew! Note: Before we dive into this article, let’s clarify a few terms computational drug-hunters use that bench chemists think of differently: ‘decoy’ – a test receptor used to perform virtual screens; ‘ligand’ – the drug docking into the protein; ‘affinity / selectivity’ – a balance of characteristics, or how tightly something binds vs. which proteins it binds to; ‘allosteric’ – binding of a drug molecule to a different site on an enzyme than the normal active site. Regular readers and fans of compu-centric chem blogs such as The Curious Wavefunction and Practical Fragments will feel right at home! We’ll start at the top. Shape complementarity modeling uses small differences in a binding pocket, such as a methylene spacer in a residue (say, from a Val to Ile swap) to dial-in tighter binding between a target and its decoy. The authors point out that selectivity can often be enhanced by considering a drug that’s literally too big to fit into a related enzymatic cavity. They provide several other examples with a ROCK-1 or MAP kinase flavor, and consider software packages designed to dock drugs into the “biologically active” conformation of the protein. Electrostatic considerations use polar surface maps, the “reds” and “blues” of a receptor’s electronic distribution, to show how molecular contacts can help binding to overcome the desolvation penalty (the energy cost involved in moving water out and the drug molecule in). An extension of this basic tactic, charge optimization screening, can be used to test whole panels of drugs against dummy receptors to determine how mutations might influence drug binding. Because target proteins move and shift constantly, protein flexibility, the ability of the protein to adapt to a binding event, is another factor worth considering. The authors point out that many kinases possess a “DFG loop” region that can shift and move to reveal a deeper binding cavity in the kinase, which can help when designing binders (for a collection of several receptors with notoriously shifty binding pockets - sialidase, MMPs, cholinesterase - see p. 534 of Teague’s NRDD review). But these...

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Drug Candidate Structures Revealed At #ACSAnaheim
Mar27

Drug Candidate Structures Revealed At #ACSAnaheim

1PM Pacific: There's one hour left before chemists will pack a ballroom in Anaheim to see potential new drugs' structures unveiled for the first time. Watch this space for updates. 2:39PM Pacific: CEP-26401 This drug candidate now has a name: irdabisant company: Cephalon meant to treat: deficits in cognition and/or attention in diseases such as Alzheimer's and schizophrenia mode of action: inverse agonist of histamine H3 receptor, which regulates several neurotransmitter pathways involved in cognition, attention, memory medicinal chemistry tidbits: Cephalon's goal was to bring a high quality compound to the clinic to define the utility, if any, of H3 antagonists for these indications. The team studied compounds in this area that failed. Among the things they learned was that several adverse events could be tied to drug candidates' lipophilicity. So the team prioritized lipophilicity and other such characteristics in its discovery workflow. status in the pipeline: completing Phase I in the beginning of April 2011, advancing to Phase II structure coming soon! UPDATED 3/29 with structure: 3:16PM Pacific: BMS-663068 company: Bristol-Myers Squibb meant to treat: HIV mode of action: inhibits HIV attachment to host cells by binding to the viral envelope gp120 protein and interfering with its attachment to host CD4 receptors medicinal chemistry tidbits: potency and getting the drug candidates to reach the bloodstream efficiently were key. Replacing a methoxy group on with heterocycles, such as triazoles, gave a big boost in potency. status in the pipeline: Completed Phase IIa clinical trials. Phase IIb studies are planned for later this year. 4:24PM Pacific:LX1031 company: Lexicon meant to treat: irritable bowel syndrome mode of action: blocks a subtype of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, in the gut. medicinal chemistry tidbits: Lexicon started their medchem program with an open mind. They could have made a molecule that was exquisitely selective for the subtype of tryptophan hydroxylase in the gut, they could avoid hitting the other subtype by making their molecule stay out of the brain, or both. They ultimately ended up using the latter strategy, making molecules slightly on the heavy side (above 500 or 550 molecular weight) and adding groups like a carboxylic acid, that tend to keep things out of the brain. status in the pipeline: Completed Phase IIa clinical trials. 5:30PM Pacific: MK-0893 company: Merck meant to treat: type 2 diabetes mode of action: blocks the receptor for the hormone glucagon. Glucagon is released by the pancreas in response to falling glucose levels. medicinal chemistry tidbits: Merck kept several chemical scaffolds in play during this research program. But the team's big breakthrough was adding a methyl group to the benzylic position of a...

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Can A Pasta King Bring Generic Drugs To Sub-Saharan Africa?
Mar16

Can A Pasta King Bring Generic Drugs To Sub-Saharan Africa?

Last week, Lisa wrote a story about India-based Cadila Pharmaceuticals becoming a partial investor in a proposed drug manufacturing site in Rwanda. This guest post from C&EN reporter Linda Wang explains another partnership in that vein. Cameroonian billionaire entrepreneur Celestin Tawamba is hoping that the enormous success he’s had in building a pasta empire in central and sub-Saharan Africa can be replicated in his latest endeavor—to establish a state-of-the-art generic drug production facility in his native Cameroon. In April 2010, Tawamba, who is widely known as “the pasta king,” launched Pharmaceutical Industrial Company (Cinpharm S.A.), in Douala, Cameroon. With financial backing from foreign investors such as Cipla, India’s largest pharmaceutical company, cinPharm has started blister packing and distributing generic drugs, including paracetamol, ibuprofen, metronidazole, amoxicillin, and cotrimoxazole. Cinpharm will also produce generic anti-malaria, anti-TB, and anti-retroviral drugs as well as drugs against gastrointestinal and other diseases prevalent in central and sub-Saharan Africa. The drugs are currently supplied in bulk by Cipla, but cinPharm hopes to one day manufacture its own pharmaceuticals. The ability to blister pack drugs in sub-Saharan African is significant because it helps to lower the cost of imported drugs, which can be extremely expensive and unaffordable for most Africans. "Local drug production may soon fill the empty shelves in local pharmacies and finally take care of alleviating chronic drug shortage," says Rolande Hodel, president of AIDSfreeAFRICA, who alerted C&EN to Cinpharm’s activities. Tawamba’s rapid rise to success with his pasta business is impressive. According to a July 15, 2009, article in the Cameroonian business journal, the Entrepreneuer, Tawamba took out a loan in 2002 and set up La Pasta S.A. in Douala, producing 25 tons of flour and spaghetti. Seven years later, the company was producing 250 tons of pasta and had employed 500 workers. With more than 300 employees and plans to hire additional scientists, Cinpharm is fast becoming one of the largest employers in Cameroon. Hodel says AIDSfreeAFRICA is supporting Cinpharm by helping to raise awareness about the company and recruit chemists with an interest in working in Cameroon. For more information about Cinpharm and other drug production efforts in Cameroon, visit AIDSfreeAFRICA’s...

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World AIDS Day Roundup
Dec01

World AIDS Day Roundup

Today is World AIDS Day. Here are some selected tidbits of basic science and business developments in the HIV/AIDS arena that we've covered in 2010. (Some C&EN links are subscriber-only). In May, Belgian scientists reported early results on the path to a new type of antiviral- one that blocks an interaction between HIV integrase, which helps the virus integrate its DNA into that of a human host cell, and a human protein that is critical for this process as well. In contrast, the FDA-approved drug raltegravir interferes with the integrase protein itself. The Belgian scientists' report, which you can read here, does not include tests on humans or animals, but it suggests that the approach of blocking this interaction, rather than going straight for the integrase itself, might be a viable option for AIDS drug development. In June, two independent teams determined what an antibody with unusually potent and broad activity against HIV strains looks like. The teams hoped this information could give a boost to the search for an AIDS vaccine. These results, which you can read here and here, are preliminary and nothing has been tested in animals or people yet. But because an AIDS vaccine would have to generate a stronger immune response to the virus than the body is capable of on its own, any clues as to how to make that immune response stronger (say, with a really powerful antibody) are welcome to scientists. In July, researchers at the International AIDS Conference in Vienna reported that a microbiocidal gel containing 1% tenofovir (brand name Viread), an antiretroviral drug, helped lower the risk of contracting HIV and genital herpes. Unlike the more preliminary work I mentioned earlier, this study was done in human patients. Also in July, Gilead Sciences announced it would close its research site in Durham, NC by the end of this year. Gilead first acquired the site when it bought Triangle Pharmaceuticals in 2003. Triangle scientists' drug discovery efforts had led to Gilead's AIDS drug Emtriva, which won regulatory approval months after Gilead acquired the business. NC-based news outlet the News-Observer had extra details on company history when the news broke: Triangle was one of the Triangle's most promising young drug companies. It was formed in 1995 by a group of former Burroughs Wellcome executives led by the late David Barry, who was a co-inventor of the first major AIDS drug, AZT. Tragedy struck the company in 2002 when Barry died of a heart attack at age 58. And finally, at August's American Chemical Society National Meeting in Boston, David S. Teager, a chemist with the Clinton Health Access Initiative, explained how...

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