The following title caught my eye…It is interesting to note that while silica-packets that accompany moisture sensitive products have a “do not ingest” warning, silica is included as an ingredient in a lot of food-products. Take a look at most powdered mixes and you will see it as an ingredient.
Martin, K. R. The chemistry of silica and its potential health benefits. Journal of Nutrition, Health & Aging (2007), 11(2), 94-98
Haven’t had time to post any article reviews so I thought I would add some more…This time Andy Myers and Wally Clever…
Paul Wender and Sam Elliott
I realize I am not the first to highlight this paper….
An interesting reaction was reported in the May 25th issue of Science. The method is touted as a new coupling method and involves an apparent Pd-catalyzed aryl cross-coupling reaction between two different “non-activated” aromatic substrates without the formation of homo-coupled products. This could potentially be a useful and expedient method for the synthesis of biaryl-compounds since it avoids the necessicity of using aryl-halide, -stannane, -borate, etc… starting materials according to the traditional transition metal coupling methods.
While I think this is interesting I am not sure this method provides a general solution to the issue of transition metal catalyzed cross-coupling of “non-activated” aromatic substrates. Setting aside the the fact that the method requires a large excess of the phenyl component, the use of indole, which is the only example inlcuded in the paper as the other component of the reaction, suggests that there is a serious limitation in scope (I must assume that other heterocyles were tried but failed to deliver the desired product) Reactions at the C3-position of indole are well known and therefore the deck seems to be stacked in the author’s favor. In addition, the authors ignore the possiblity that Pd(II) might be acting as a Lewis acid. As I show below, Tajima and Nakatsuku have shown the same transformation is possible using AlCl3 and MnO2. Granted this is not catalytic but it shows a parallel mechanism without the
There is a striking resemblance between Nobel prize winning chemist R B Woodward and former US-president Lyndon Johnson….Coincidence???
It’s rare that a disease or disorder can be attributed to a single mutation in a gene let alone to a single gene but in certain cases such as in Cystic Fibrosis and Rett syndrome this is exactly what happens. If you were able to find the gene that was responsible for such a disease you might think that you were well on the way towards developing a treatment or cure, but this has proved not to be the case. The problem lies in the fact that the mutations that are often associated with disease usually lead to “silencing” of a vital protein, be it an enzyme or receptor, meaning that the protein is non-functional or is not expressed at all. Medicinal chemistry is only good at modulating (ie. inhibiting or activating) proteins that work normally so there is a fundamental problem in dealing with proteins that don’t work correctly or are not even present.
That is why a recent paper in the May 3rd issue of Nature caught my attention. In it researchers from PTC Therapeutics describe a small molecule PTC124 which is able to resuscitate a protein which contains a mutation that prevents it from being synthesized.
The gene in question is dystorphin which is involved in Duechenne muscular dystrophy and the mutation is a so-called ‘nonsense’ mutation which acts as a mRNA stop signal inhibiting the complete translation of the protein.
Earlier experience with the aminoglycoside Gentamycin showed that it was possible to use a small molecule to suppress the ’stop’ signal on an mRNA leading to synthesis of the complete fully functional protein. Unfortunately, this compound showed poor in vivo efficacy and was associated with toxic side effects.
A screening effort led to the discovery of PTC124, a remarkably simple looking molecule that was more amenable to drug development. The compound effectively suppresses the stop mutation in cell culture and in mice expressing the mutation. It is currently in clinical trials and the FDA has granted it fast track designation as a potential treatment for Duechenne muscular dystrophy and/or cystic fibrosis.
I am busy with a number of projects and have not had the time or energy to keep up. I have set aside a few articles over the last week or two which I will try to post soon but until then a few random thoughts…
Developing drugs to treat Autism…
In addition to my primary field of research I have been tracking the field of Autism research on the side. In fact, I hope to complete a review on potential drug targets which might be effective for treating the core and/or secondary symptoms.
…what I have found is that apart from the work being carried out in academia very little is going on in industry especially at the major pharmaceutical companies. In order to get a feel for how little is being done, I was not able to find “autism” mentioned once when I searched The Journal of Medicinal Chemistry using SciFinder. This is a little disappointing but perhaps understandable given what little is known about the condition.
Recently, things have begun to change…newer estimates suggest that a lot more people are affected than previously thought which was one of the reasons the US-government targeted it in the ‘Combating Autism Act of 2006′ which freed up close to a billion dollars to fund screening, education, early intervention, prompt referrals for treatment and services, and research.
I’ll discuss potential drug targets in the future…
Single payer healthcare in the US….
I think that unless something major happens to change people’s minds that a single payer drug benefit for Medicare is inevitable in the next few years. If this happens it might not take too long before more momentum builds for nationalized health care coverage. This has a lot us in the pharmaceutical business scared since under the single payer system the government will have a lot more leverage to negotiate lower prices which could mean lower profit for the pharmaceutical companies.
Granted, I am not very knowledgeable when it comes to business and economics but I think that a single payer system for drug benefits will probably not end for the pharmaceutical business. I believe there is money to be made under such a system if companies change the way they do business. It might be ironic, but most of the today’s large pharmaceutical companies got to their big break by manufacturing antibiotics for the government during WWII.
I realize tough times might be ahead of us but being the optimist that I am, I have listed what I think are some of the potential positive aspects of having a single payer system:
1) A single payer system might take some of the uncertainty concerning price and top-line revenue out of the equation, making investors and CEO’s a little less jumpy.
2) While lower prices will impact the top-line in a negative way they might reduce the costs of marketing a drug freeing up money for research and internal investment.
3) Lower prices might hold off some of the generic companies when a compound comes off patent since the lower price will impact theircost/benefit calculations. If the government has the power to negotiate a lower price from the innovator….. they should be able to get an even lower price from the generics since their cost base is much lower.
4) Drugs have a better cost-benefit ratio than other types of medical intervention which might mean that given the choice the government might start directing a higher proportion of federal dollars to drugs under a single payer system.
I have nothing against pharmaceutical company ads and in fact feel that they empower patients and help them decide what is best for themselves with the advice of their doctor.
However, I do have a problem with famous physicians appearing in the media hawking a particular drug. Such is the case with the Dr. Robert Jarvik’s Lipitor ads (note: I am not sure these adds are seen outside of the USA). Does the average layperson realize when they see such an ad that what Jarvik is telling them is coming from Pfizer and that he is being payed to say what he is saying?
At least with famous athletes, acting as spokesmen/spokeswomen for a product, you realize up-front that they are being used by the company to get your attention and that what they say comes from a script developed by the ad agency…I mean does anyone believe that Tiger Woods is an expert on cars, watches, sports clothes, etc…
With Jarvik you might assume that what he is saying comes from his expertise and that he has your best interest in mind. But that would be wrong since the whole idea behind advertising to advance the interest of the company.
I think most people are smart enough to see through this, which concerns me even more, since it just adds to fodder to the poor image of pharmaceutical companies that has emerged in the last decade.
P.S.I think Lipitor is a great drug since it appears to lower cholesterol to a greater extent than its predecessors. It also proves the point that there is always a need and room for improvement in existing drug classes despite being cast as “me too drugs”
I wrote awhile ago about idiosyncratic reactions and the challenge they pose to drug researchers. Perhaps one of the biggest challenges which is some ways might be considered a blessing is that, thanks to extensive pre-clinical testing and rigid regulatory standards, the number of incidences of adverse drug reactions is very low making it difficult to develop a sufficient body of data to determine the mechanism of the reaction. However, at this point in time, we have methods for investigating the genetic profile of patients and thus the potential exists to correlate adverse reactions with a genetic signature, but only if we have enough patients to work with.
A commentary in the April 26th issue of Nature describes a potential solution to the problem of lack of data….increasing the rate of adverse event reporting and pooling the data in a global database.
And now for something completely different…..
For anyone out there who teaches first year organic chemistry…the discussion by Euripides G. Stephanou of the paper published by Williams et al., which describes the chiral make-up of compounds released from forests into the atmosphere might make an interesting side bar example when the subject of stereoisomers is introduced.
Derek Lowe’s, “In the Pipeline“, had an interesting discussion on animal models and their ability to predict the efficacy of drugs in people…
Interestingly from what I have observed, being in the area, is that the success rate in the clinic of antiviral drugs against HIV, at least in the context of efficacy, is very high despite the fact that there are no animal models.
That’s right…what most people outside of the field might not realize is that the only pre-clinical “efficacy” model used for HIV drugs is cell culture antiviral activity. In almost every case bona fide activity in cell culture translates into clinical efficacy. The only thing standing in the way of a cell culture active compound and a clinical candidate is the usual ADME-Tox studies, but cell culture activity is usually (but not always) good enough to provide drug-like compounds. The caveat is that the anti-viral activity must be validated in order to weed out the “promiscuous” false-positive compounds.
This might be the reason that a lot of start-up companies are pursuing anti-HIV agents even thought the market is becoming very crowded (>20 drugs and counting)
