Chemistry and Life

Medicinal chemistry. Pharmacology. Toxicology. Environmental sciences.


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What drugs are being used experimentally to treat ebola?

With ebola in the news so much these days, I became curious which pharmaceutical drugs are being used to treat patients. I haven’t come across the information in any one place, just scattered among news articles and other sources. So I decided to put together a list myself. There aren’t any drugs approved specifically for treating ebola, but apparently several antiviral agents are being used experimentally. They are mostly drugs developed (or in development) primarily for treating other viruses.

    • Brincidofovir (CMX001) – An experimental antiviral agent which is a prodrug of the approved HIV medication cidofovir (Vistide). It belongs to the class of drugs known as nucleoside analog. The first person with ebola in the United States, Thomas Duncan, received this drug.
    • Favipiravir (T-705) – This is an antiviral agent that has activity against a variety of viruses. It is approved in Japan for use against influenza.
    • Lamivudine – HIV drug used in Liberia
    • ZMapp and ZMab – Related monoclonal antibodies. Both have been used in ebola patients in the United States and in Spain
    • BCX4430 – Experimental broad-spectrum antiviral and nucleoside analog. The National Institute of Allergy and Infectious Diseases (NIAID) is funding additional research and drug production.
    • TKM-Ebola – Has been used in one patient who was infected in Africa and brought to the United States. It is a combination of small interfering RNAs.
    • JK-05 – Several news articles describe this as “an experimental anti-Ebola drug developed by the Chinese military” that is “already approved for emergency military use” and has been sent to Africa, but I can’t find anything specific about what exactly it is or whether it is actually being used yet during the current outbreak
    • FGI-103, FGI-104, FGI-106 – I haven’t found any news references to these compounds currently being used experimentally during the current ebola outbreak, but there are animal studies reported in the corresponding Wikipedia articles

There are also vaccines such as VSV-EBOV under development.  These can’t be used to treat infected patients, but are instead intended to prevent the spread of the disease.

If I have missed any other drugs that have been mentioned in the news but aren’t on this list, please let me know and I’ll add them.

 

 


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Forces that hold rapidly spinning near-Earth asteroid together discovered — ScienceDaily

Chemists are used to thinking about things on a very small scale. Sometimes, though, we think about how molecular interactions have tangible or visible effects on the properties of materials. But we don’t often think about how interactions between molecules can have much larger effects, like determining the fate of an entire astronomical object. Here’s story to remind chemists to think about the big picture:

Forces that hold rapidly spinning near-Earth asteroid together discovered — ScienceDaily


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How do tick bites cause allergy to red meat?

I’ve seen reports of this in the news a few times lately:  some people can become allergic to red meat after being bitten by a tick.  (See here or here, for example.) We are not used to thinking about allergic reactions this way. We think of sensitization to an allergen due to repeated exposure to that allergen. Peanut allergies come from exposure to peanuts, for example. So why does exposure to a tick bite sometimes lead to becoming allergic to red meat?

The connection is a carbohydrate called galactose-alpha-1,3-galactose, or just “alpha-gal”. Alpha-gal is present in the tissues of mammals, with the exception of primates (including humans). When a tick bites an animal, some alpha-gal then gets into the tick. When the tick bites a human, the alpha-gal is transferred through the tick’s saliva into the individual who is bitten. The bite, or perhaps a component of the tick’s saliva, triggers an immune response that results in the alpha-gal being recognized as a foreign substance leading to sensitization to alpha-gal upon later exposures. Since alpha-gal is present in animals, particularly those from which we get red meat, an individual who has become sensitized to alpha-gal has an allergic reaction to eating red meat.

In the United States, the problem seems to be closely associated with only the Lone Star Tick, which has a limited range mostly in the Southeast. The problem doesn’t appear to be currently widespread.

For details on how the cancer drug cetuximab was the key to discovering the connection between tick bites and red meat allergy, the paper titled “The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose” makes a good read.


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Cleaning up polluting mines with plants

Here’s a nice write up describing a project that uses plants to clean up a polluted mine site, a process called phytoremediation. In this case, the possibility of harvesting plants that have accumulated metals and then recovering the metals for profit (“phytomining”) is being explored.

Cleaning Up Polluting Mines With Plants–Plants That Then Turn Into Precious Metals


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Bisphenol S is replacing bisphenol A (BPA), but is it any safer?

Bisphenol A (BPA), a chemical used in some types of plastics, has gotten a lot of public attention in recent years because of its estrogen mimicking effects and the public’s widespread exposure to it. Many manufacturers have removed BPA from products which come into contact with food, and in some jurisdictions there are now regulations limiting its use.

One of the chemicals that is used as a replacement for BPA is bisphenol S (BPS). BPS is chemically related to BPA and actually has the same inherent estrogenic activity which is problematic in BPA. However, BPS was thought to be a safer alternative because, it was claimed, it did not leach from plastics like BPA does.

That belief is now being questioned. An article at Scientific American details some of the research and concludes that the real issue behind the public safety problem is not so much that we can’t determine the health concerns associated with a particular chemical but that, “Currently, no federal agency tests the toxicity of new materials before they are allowed on the market.”


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Why are there so few boron containing drugs?

TavaboroleThe antifungal drug tavaborole was approved by the FDA a few weeks ago. One thing that is unusual about the chemical structure of tavaborole is the boron atom that it contains. Boron is not a common element in pharmaceutical drugs. The cancer drug bortezomib (Velcade) comes to mind, but there aren’t many. The antibiotic compound boromycin contains boron too, but it’s not a marketed drug.

So what’s wrong with boron that prevents its widespread use in pharmaceuticals? As far as I know, and also according to a review in EMBO Reports, there is nothing inherently bad about boron in terms of it being used in medicines. It seems to be that medicinal chemists simply don’t try to use it often.

The company that developed tavaborole, Anacor Pharmaceuticals, is trying to take advantage of this omission. Their whole pipeline of drug candidates are relatively simple organoboron compounds. You can carve out some novel chemical space in terms of intellectual property that way.

I have encountered a similar situation in my career, except instead of an underutilized element, it involved an underutilized functional group. In developing the anticonvulsants JNJ-26990990 and JNJ-26489112, we were able to patent some very simple* compounds because they contained the relatively uncommon sulfamide functional group. We encountered no inherent problems with druggability associated with the sulfamide groups, and noticed that it showed up relatively infrequently in the patent literature, so we came to the conclusion that it was an underappreciated and underutilized functional group in medicinal chemistry.

*Readers in the drug discovery field can imagine how pleased our scale-up group was to learn that our first clinical candidate could be prepared in one step from commercially available materials.


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A contrarian view on the cost of sofosbuvir (Sovaldi)

There has been a lot written about the cost of Gilead’s new hepatitis C drug, sofosbuvir (Sovaldi). Most of the discussion has been highly critical of the price and Gilead’s stated justifications for it. Here is a contrarian view:

Each of these Hepatitis C pills cost $1,000. Thats actually a great deal.