Shedding Light on Cancer Cells

Quyen Nguyen is a surgeon at the University of California, San Diego who has worked with chemists to develop molecular beacon type dyes that light up when they come into contact with cancerous tissue or nerve cells. This could give surgeons a sort of chemistry-based augmented reality, showing them exactly where and where not to...

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Juan Enriquez Eviscerates the FDA

In this lecture, tech investor Juan Enriquez explains how the FDA’s extreme risk aversion hurts us, and why that behavior is our...

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Using Gene Expression Patterns to Repurpose Drugs
Nov14

Using Gene Expression Patterns to Repurpose Drugs

Late last month, researchers from many different fields gathered at the Computer History Museum in Mountain View, California, to discuss the benefits of open science and data sharing. One of the best talks from that event, the Open Science Summit, was delivered by Joel Dudley, the co-founder of NuMedii, a firm that aims to find new indications for medications. Dudley has repeatedly found new uses for old drugs by picking through public data sets about the gene expression profiles of different diseases. He then looks for medications that are known to reverse those profiles. Much of the data that Dudley uses comes from the Gene Expression Omnibus, which he regards as a gold mine. Life Sciences in the Era of Big Data from Open Science Summit on FORA.tv A full list of videos from the Open Science Summit is also...

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Beating Trypanosomes
Aug01

Beating Trypanosomes

Above: Triatoma sanguisuga, a bug that carries Chagas disease. Photo by Jim Gathany / Arizona Department of Health Services Late last week, a group of researchers from the University of Ibadan in Nigeria published a paper (Parasitology Res., DOI: 10.1007/s00436-011-2516-z) on several herbal extracts that can kill the parasites that cause sleeping sickness. Unfortunately, important projects like that are few and far between. I’m almost done writing an article about drugs in development to treat sleeping sickness and Chagas disease, a pair of illnesses caused by a class of protozoans called trypanosomes. My story explains that the current treatments take several weeks, and the drugs have a wide variety of side effects ranging from rashes and headaches to neurological damage and death. One of my sources seemed to be overly confident that better treatments for these diseases are just around the corner based on the early performance of several compounds that are in clinical trials.  I’m not convinced. Not long ago, a compound codenamed DB-289 entered Phase III trials for sleeping sickness. Everything seemed to be going well. And then, suddenly, the trial was halted due to safety concerns. A handful of promising new drugs are making their way through clinical trials, and a few academic labs are looking for new compounds that can kill trypanosomes. Here is a roundup of some of those substances: Phthalazines A recent improvement upon the series of phthalazines developed by Manuel Sanchez-Moreno, Fernando Gomez-Contreras, and their colleagues in Granada, Spain. Very early stage, Chagas disease DDD85646 Identified by an academic library screening project, this compound inhibits N-myristoyltransferase in the trypanosomes that cause sleeping sickness. Preclinical, sleeping sickness SCYX-7158 An oxaborole similar to the ones developed by Anacor pharmaceuticals, a company that is testing boron-based drugs for a wide variety of antimicrobial applications. Late stage preclinical, sleeping sickness. K777 An inhibitor of the protease Cruzain, developed at UCSF, it may enter human trials within a year. Late stage preclinical, Chagas disease Posaconazole Already on the market as an antifungal drug, it kills T. cruzi in vitro tests. Preclinical, Chagas Fexinidazole Developed by Hoechst and shelved, DNDi resurrected this broad-spectrum agent. Phase I, sleeping sickness. E-1224 Eisai developed this azole prodrug as an antifungal agent. It is formulated as a monolysine salt. Phase II, Chagas disease DB-289 Proved effective, but trials were halted after participants showed signs of liver toxicity and renal insufficiency. Phase III, sleeping sickness Sleeping Sickness Drug Targets Pteridine Reductase, N-myristoyltransferase, Trypanosome alternative oxidase, BILBO1, glycosylphosphatidylinositol membrane anchors Chagas Disease Drug Targets Lanosterol 14α-Demethylase, Superoxide Dismutase, cytochrome P450 sterol 14-demethylase, Cruzain Here are some great sources of further information. All about diagnostics...

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Sensible Antisense RNA Modifications
Jun23

Sensible Antisense RNA Modifications

This is the first Haystack post from C&EN Intern Aaron Rowe. You may recognize Aaron from Twitter (@soychemist) or from his contributions to WIRED and its science blog. Isis Pharmaceuticals showed off its latest strategy for improving the potency and pharmacokinetics of antisense oligonucleotides at its annual shareholder meeting, held last week. Their structure, called cET (structure at bottom right), should bring the size of a dose down to 5-40 mg per week and allow oral delivery of antisense molecules for some diseases. In its drugs, Isis uses a mix of several different modifications. They call these molecules gapmers. For instance, its cholesterol-lowering phase 3 compound, mipomersen (molecular model at top), has 2’-methoxyethyl modifications on each end (see structure at bottom left) and central DNA region, and it also has a phosphorothioate backbone. The newer cEt modification will be featured in a cancer drug that targets STAT3, a transcription factor that is overactive in many different malignancies. Here’s more on the cET...

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