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A Few Days Off (Bonus Blog Topic Thread)

I wanted to let people know that posting will resume here this coming Wednesday – I’ll be traveling, and I probably won’t have time to put up any entries. If something big happens, I’m sure I’ll work something in, but otherwise, I’ll see everyone on the 19th!

In the interim, I’d be glad to hear blogging suggestions from everyone in the comments to this post. I have some topics queued up, as usual, but it would also be valuable to hear about what people would like to hear about. Thanks!

60 comments on “A Few Days Off (Bonus Blog Topic Thread)”

  1. Jurgen Bosch says:

    How the field is developing towards protein-protein interaction inhibitors and stabilizers. There have been quite a few drugs approved. And since you worked for Vertex, one can consider the VX809 as a PPI stabilizer between two domains of CFTR.

  2. Paul Bristow says:

    As a long time lay reader of this blog, and also a long time maker, I’d be curious to see what you make of the bio-hackerspace community.

      1. Paul Bristow says:

        That would be nice 🙂

        Was thinking more like http://biocurious.org or http://www.hackuarium.ch/en/

  3. Doug says:

    Compounds I’ll never work with. Please sir, can we have another? (and where’s the book full of chemical mayhem?)

    1. cato says:

      Did you ever cover those fluoroxy compounds that gained some prominence when Barton used it to make 5-fluorouracil?

  4. anon says:

    How about an autobiographical post? It would be interesting to hear about your education and career stories in a long blog post.

  5. Hap says:

    A tellurium (compound) “Things I Won’t Work With”?

    1. Cato says:

      or perhaps a beryllium one too?

    2. David says:

      More things I won’t work with!
      For the book…

  6. anonymous says:

    Theranostics..this field seems to comes up big but fails eventually!

  7. Christophe Antczak says:

    Impact of NIH funding cuts on drug discovery. Should Pharma lobby more against them, since it is in their own interest?

  8. gm says:

    your current experience with job hunting?

  9. NMH says:

    Compounds I wont work with which include stories of death, dismemberment and other assorted mayhem. Whether I like it or not, my Org Chemistry lectures are listened to carefully when I tell stories of Org Chemists getting injured (eg Barry Sharpless).

    1. Daniel Barkalow says:

      “Things I won’t work without”?

      1. Ken says:

        I like this one. Favorite reactions/reagents.

      2. dp-mcgill says:

        THF, DCM, toluene, ethyl acetate, hexanes, magnesium sulfate, triethylamine, potassium carbonate, silica. Riveting!

    2. sleepingatscripps says:

      One of the worst stories I’ve heard is Saul Winsteins students dying from exposure to a chemical they synthesized, and another being hospitalized. Somehow hardly anyone knows this story, and it’s a good lesson for why you should use gloves and a fumehood at all times (whether or not that would have spared Winstein’s students, I cannot say).

      1. Metacelsus says:

        For more information about the poisonous compound, here is the relevant paper:
        pubs.acs.org/doi/abs/10.1021/ja01467a058

        “of the three laboratory workers who have used the dibromides and bromohydrin VII, two later developed similar pulmonary disorders which contributed to their subsequent deaths. The third has exhibited minor skin sensitivity reactions.”

        1. milkshaken says:

          “Magic methyl” MeOSO2F put few students in intensive care with lung edema, and TMS-diazomethane killed a technician in Canada; he used it in scale up while fume hoods were shut off for maintenance. Nasty genotoxicity and pulmonary toxicity of epichlorohydrine has been known for a long time. Also ethylene oxide is quite insidious, as it does not possess much of an odor.

          1. Nick K says:

            Magic Methyl actually killed a guy in the Netherlands some 35 years ago. He dropped a flask containing about a gram of the substance, and a few drops landed on his sweater. A few hours later he was dead from pulmonary edema.

          2. nattle says:

            I had to correct an undergrad once who was haphazardly holding a TMS-diazomethane bottle by the cap (with her bare hands), while walking around the lab looking for something. Her response to my suggestion to be a little more careful was “but it’s the TMS one so it’s safe”.

  10. Chemcat says:

    How about a post covering in vivo Magnetic Resonance Spectroscopy (MRS)? Readers here are likely familiar with other magnetic resonance methods, like NMR and MRI. However, they might not know about MRS and why it is an exciting technique for non-invasively studying disease states (especially in the brain) and effects of potential treatments in living animal models and humans.

    Discussing some roadblocks to using MRS in the clinic and in therapeutics development would make for a balanced evaluation of the field as it is now (pun intended). Might be interesting to cover the prospects of using MRI/other imaging modalities as secondary outcome measurements in drug trials, too (i.e. how often do folks actually include MRI outcomes in their clinical trial designs?).

    1. cynical1 says:

      They use Gd-enhance lesion formation in multiple sclerosis all the time in MS trials.

      1. Chemcat says:

        Ah, thank you!

  11. NJBiologist says:

    I’d love an update of the what-code-goes-with-what-company list. Mundane, I know, but still useful.

  12. Chrispy says:

    I’d love an update on how the “open office” concept is playing out for drug discovery. Many of your readers have had a couple of years of experience with this, so the story could be largely comment driven.

    And here’s a story about how Apsen drove up the price of cancer drugs in Europe:
    http://www.independent.co.uk/news/health/drug-giant-aspen-plot-destroy-cancer-medicine-big-pharma-times-investigation-a7683521.html

  13. The hard ones says:

    Maybe a post about how hard your substrates should be in order to get an academic job.

    1. Gimmi De Beers says:

      I’m unsure if the hardness of the substrates is that important, as I’m struggling to find an academic position despite focusing on diamond research.

  14. J Severs says:

    Things I learned in the pharma (or real world) that I wished I had known while an undergraduate or graduate student.

  15. Mol Biologist says:

    It would be great to review most challenging : What is a key component of success in modern drug discovery. Have a safe travel and thank you again for doing great job with your blog.

    1. Mol Biologist says:

      Things I learned life never stops and always one is here to be next, after Graphene the super materials that could trump graphene is almost there. http://spectrum.ieee.org/semiconductors/materials/germanium-can-take-transistors-where-silicon-cant

  16. Anon anon anon says:

    Reproducibility: biology (cancer cell lines, etc) sure, but also chemistry. What should we expect to reproduce from two synthetic papers? How much do two binding assays correlate from the same lab? From two different labs? From two different assays?

  17. Monsieur_Maladroit says:

    CRISPR update – there have been plenty of new techniques added (gene drive, potential medical applications) and legal proceedings to cover.

  18. Gene says:

    In vitro rock star compounds that totally tanked in vivo.

    1. Anon says:

      See: Alzheimer’s research

  19. RT says:

    Industrial chemical synthesis in microgravity.

    1. zero says:

      I’ll second that and raise you this: Is there a feasible set of equipment and (recoverable) reagents that could allow one to synthesize medically useful compounds in an off-planet outpost?
      In other words, on a sliding scale between total freedom and total dependence on resupply from Earth, where are we at with current tech?

  20. Daniel says:

    I’d love to read about your views on prebiotic chemistry/chemical evolution subjects if this is a topic you’re interested in.

    Daniel

  21. gippgig says:

    What chemicals do you keep in your house/car? For example, I have a box of baking soda (sodium bicarbonate; in case the battery explodes) and a bottle of citric acid (if I have a base shouldn’t I have an acid? – citric because I use a solution of it in a spray bottle at home as a soap scum buster) in my car. I carry a spray bottle of hydrogen peroxide (standard 3% solution) with me (general purpose cleaning/sanitizing).

    1. Mark Thorson says:

      To a cop, you’re either a drug cook or a terrorist.

  22. dearieme says:

    When I was young I was taken by Dasent’s book Nonexistent Compounds: his proposition was that you can learn useful chemistry by asking why doesn’t compound X exist?

    Here’s a paper discussing some of the non-existent compounds that had later become existent.
    http://cmacd.myweb.cs.uwindsor.ca/Teaching/651-class/651-NonExistent1.pdf

    Here’s something more recent on “NONEXISTENT COMPOUNDS AS A GUIDE TO INNOVATION
    http://scholarcommons.usf.edu/cgi/viewcontent.cgi?article=1003&context=chm_facpub

    1. Anonymous says:

      Similar thinking has influenced many others. (1) The inside covers of Hendrickson, Cram and Hammond’s Org Chem texts had lists of “difficult” (impossible?) compounds not yet made … and future editions had updates on those made since the previous edition. (2) Cyclopentanone was once thought to be an impossible, too-unstable compound because no one could synthesize it rationally. Then, it was isolated from a wicked hot natural products degradation. (3) I sometimes think that Corey was influenced by a desire to invent “impossible” reactions. Umpolung turns pos to neg and so on. (I think Dave Evans had an early unpublished paper on polarity and polarity reversal.) (4) As many are aware, fullerenes and nanotubes were proposed long before they were ever found in the lab. (5) Roald Hoffmann has written some papers on “interesting” compounds that can stimulate further research.

      (6) Anyone in med chem has probably been asked to make plenty of non-existent and impossible to make compounds by their biologist, computational and other colleagues (and bosses). “We need you to put a hydrogen bond acceptor over here.” “Can you keep the aromaticity but put a methyl group over here?” And you would all recognize the sometimes paradoxical, self-immolative, oxymoronic aspects of many such requests.

      I’ve kept lists of my favorite non-existent compounds. They ARE (or should be) very stimulating.

      1. dearieme says:

        Hammond. That rings a bell. From very long ago.

        1. Anonymous says:

          George S. Hammond. Hammond Postulate (transition states; reactive intermediates).

      2. Antipodone says:

        “Cyclopentanone was once thought to be an impossible, too-unstable compound because no one could synthesize it rationally. Then, it was isolated from a wicked hot natural products degradation. (3)”
        I assume you mean cyclopropanone

        1. Anonymous says:

          Whoa! Thanks for catching my error but I meant to write cyclopentane-1,3-dione.
          Quoting from Woodward (that’s a name that has come up recently.) “C-1,3-d provides an instructive elementary example in this respect. After the compound had eluded a number of plausible synthetic attempts, many chemists were tempted to conclude that it must be an unstable substance … Yet, when it appeared on the chemical scene, … it was produced by the action of boiling HCl and red phosphorus on a degradation product of aureomycin.”

          1. GIAnon says:

            Now that’s something I don’t want to work on!

    2. Anonymous says:

      While clarifying the cyclopentanone – cyclopropanone – cyclopentane-1,3-dione issue, above, I came across: “Chemical Squonks”, Chemical Innovation, 2000, 30(4), April 2000, pp. 24-32. ISSN 1527-4799 CODEN CINNFJ

      To a rough approximation, chemical squonks are sad, unstable compounds, sometimes crying to the extent that they dissolve, autocatalytically, in their own tears.

  23. Interest in automation says:

    I would really appreciate an article that covers “The future of drug discovery” including trends such as automation, globalization, outsorcing, biologics etc as well as how to position yourself in a way that you keep having a good job in this field.

  24. Roboticist says:

    As a computer scientist, I would like to read an article that talks about protein dynamics in silico and how it is applied to drug discovery.

    How much good are MD models doing? How do drug discovery chemists regard motion planning techniques? How about more exotic techniques, such as L. Tapia’s diffusion simulation for modelling antigen binding?

    After all, if those aren’t being used, I should probably apply my robotics knowledge to prosthetics.

    1. Curious Wavefunction says:

      Roboticist, you might want to read Anthony Nicholls’s critique of MD in drug discovery which makes some valid points.

      http://blog.eyesopen.com/ant/2013/11/26/cd-and-md/

  25. Busby's Flat says:

    Since you ask, afamelanotide. It’s gone to market in the EU, going to the FDA this year, and I would value any informed comment.

  26. Busby's Flat says:

    Since you ask, afamelanotide. It’s gone to market in the EU, goes to the FDA this year, seems largely derisked to me, and I would value any informed opinion.

  27. Mister B. says:

    I would enjoy any article related to drug pricing in general. Sovaldi’s price still echoes in Europe and I would like to know more about this ! (And drug pricing in general)

    Have mentalities evolved in good or bad way ? And closely related, but, what is changing in the patent area when a mega-merger between big-pharmas happened ? Does it change the drug pricing ?

    1. Sulphonamide says:

      I’d (and my students) would really like to know how much people in the USA actually pay for drugs like sofosbuvir (after all these confusing co-pays and rebates and whatever else) – and likewise how much of the list price the insurance companies pay pharma.

  28. David says:

    There are two articles recently that are not exactly related to chemistry (directly) but certainly will have an affect on the pharmaceutical industry if they pan out. The first is:
    http://gero.usc.edu/2017/02/23/fasting-mimicking-diet-may-reverse-diabetes/
    which was published in Cell.
    The other is the rumor that Apple has a secret project that has found a way to measure blood sugar without puncturing the skin (or using test strips). Both (if true) could have an enormous monetary affect on the the industry.

  29. LiqC says:

    It would be interesting to hear you weigh in on utility (or futility) of academic and industrial carbon capture activities.

  30. Super glad to hear of your return. I’d be most interested in a bird’s eye view of how to increase research and motives for enhancement vs. disease model studies. As Nick Bostrom outlines, a 1% boost in cognition for all scientists can increase output as if we had 100,000 more scientists. Theoretic at best, but still something that interests me.

  31. GIAnon says:

    How hard would it be (TM) to generalize this compound for all hemagglutinin types, and/or work this into a safe/effective drug? (As a layman, this sounds like a silver-bullet, and I think you could pour some cold water on these dreams in your inimitable entertaining style.)

    https://arstechnica.com/science/2017/04/south-indian-frog-oozes-molecule-that-inexplicably-decimates-flu-viruses/

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