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  • scistats scistats Oct 28, 2013 9:23 PM Flag

    Anybody following the Merck molecule 19 story?

    Merck struck out with 19

    1. 19 metabolized to 26
    2. 26 has no effect on pain
    3. 19 also has several drug metabolism related issues including inhibition of CYP3A4 enzyme, activation of
    PXR, and the significant formation of the circulating metabolite 26 in vivo.

    Looks like Terry's molecule stays intact through metabolism and does not alter enzyme function. Merck tried to develop their own chemistry and failed, at least with molecule 19.

    Sentiment: Strong Buy

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    • Buried beneath a sea of paperwork, scientific journals and textbooks, UBC Vancouver molecular neurobiology researcher Dr. Terrance Snutch keeps a box of brightly patterned cone snail shells. These are no ordinary shells; their fragile, diminutive structures potentially hold the secret to efficiently alleviating chronic pain in humans.

      “Cone snails are these beautiful shells from the South Pacific,” reveals Snutch, handling them with delicacy. “This is where the peptide Prialt comes from. It blocks pain receptors and it’s very efficacious in easing human pain.”

      Just how efficacious, no one could have ever dreamed. The peptide in the snail’s venom, which even surpasses the potency of morphine, prompted scientists to frantically investigate the potential for a new category of drugs that lack the addictive side-effects of traditional painkillers. Initial scientific efforts resulted in Prialt, a drug that blocked pain receptors. Although Prialt was effective at alleviating pain, it proved to be an invasive treatment that required injections into the spinal cord through a pump implanted under the skin.

      This lack of effective application of the snail’s painkilling agent prompted Snutch to take a drastically different approach: “My idea was to develop a drug that you could take as a pill that would work like Prialt,” he explains. “NMED-160 is an orally-made available drug that targets the N-type channel.”

      The new direction paid off for Snutch in a big way. Last year, his UBC spin-off biotech company – Neuromed Pharmaceuticals – struck a record partnership deal with Merck & Co. to develop and market the painkiller NMED-160. Valued at nearly $500 million USD, it is the richest collaboration for a drug in development ever in Canadian history.

      “It turned out that out of the 22 pharmaceutical companies we talked to, pretty much all of them – 19 out of 22 – were interested,” says Snutch. “It came down to Merck being the best opportunity: absolutely outstanding scientist

    • Compound 19
      Molecular Weight: 547.58
      tPSA: 88.59

      Prognosis as a CNS agent...poor

      • 1 Reply to ike_tike
      • OK, this is as I thought--ike and sci are very likely the same person who hasn't much understanding of the papers and articles that he or she is copying and pasting from. What I'm reading in this thread is a lot of nonsense, and anyone with the same background and training can see it too.

        Since the point of this little fraud is to gain undeserved expert status, and that in turn can only be meant to serve some kind of manipulation, I'm putting these aliases on "ignore."

    • For clarity's sake, the molecule in question (19) didn't "metabolize to" the unwanted sulfonamide. The latter was just one metabolite, albeit a problematic one. Also PXR activation generally induces 3A4 not inhibits. That's a very minor DDI issue. About half the drugs out there metabolize through 3A4 so you would have competition for that enzyme, but that's not at all unusual.

      I'm not sure what your CV looks like, sci, but I'm guessing you're not formally trained. You a hobbyist?

      • 1 Reply to rul6t2
      • For clarity's sake:
        1. Figure 5 of the 2012 paper, 19 --- Metabolism ---- 26.
        2. Compound 19 inhibits CYP3A4 enzyme.

        rul6t2, do you drive a large truck because normally when people's tone turns to putdowns, it says a lot about a man. By the way, have you published in Nature recently :)

        Sentiment: Strong Buy

    • Reference J. Med. Chem. 2012, 55, 9847−9855

      Sentiment: Strong Buy