Rational Drug Design

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When one thinks about drug research, they rarely recognize that it’s often just a series of trial and error.  One considers a series of potential drugs and determines if and how it works.  Rational drug design is a completely different (and still a nascent) process.

For the rational drug design process, we know the biological target and how it operates.  So, we see a small molecule that can activate or inhibit the function of the target (typically a protein), thereby affording a therapeutic benefit.  The initial choice is to employ a compound that is complementary in shape (and a few other characteristics) to the target, affording interaction and binding with it.

Well, this process is being elevated to a whole new scale by Parabon, a small company from Northern Virginia.  The company received some initial funding for this process from the National Science Foundation SBIR (Small Business Innovation Research) program.  A provisional patent was filed in May 2011 and the final application was published in 2012. The first drug rolling off their platform is one that will be used to treat brain cancer, glioblastoma multiforme.  (This is the cancer to which Ted Kennedy succumbed).

The process employs a computer  “drag and drop” process with DNA self-assembly.  (Parabon calls this their “Essemblix” Drug Development Platform.)  In essence, the compound is “printed” molecule by molecule.   Truly the definition of rational drug design.  Trillions of identical copy of the molecules can be assembled, over the course of days or weeks.  Using the principles of 3D printing for biomolecular production.

The process is fairly simple. Using a programmable molecular substrate,  the DNA is sequenced in particular order so that single-stranded DNA can be formed.  Using molecules that can attach to various portions of the “body” of the strand, the therapeutic agent can be incorporated into the self-assembled drug.  The smaller strands then are coalesced into larger macromolecules, ready to be administered to the patient.

The drug is currently termed P24RDN.  It has completed its preclinical studies, with indications for better patient survival from the intracranial glioma tumors.  In addition to this application, Parabon is working on a prostate cancer drug (PJ-01, in partnership with Janssen Pharmaceuticals), synthetic vaccines (biodefense), among others.  The same technology is also being used for non-medical applications (molecular nanosensors and nanoscale logic gates).

Another 3D printing success concept.

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31 thoughts on “Rational Drug Design”

  1. This is very interesting on more than one level. I had no idea how they went about with their research. All we ever hear about are the mice. Are they trading on the NYSE, it sounds like a possible good investment.
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  2. This is exciting news, Roy!! My husband’s best friend, his wife died of a glioblastoma in 07, and you know my husband had prostate cancer so I’m thrilled this is happening! Our clinical trial drug was an CNTO 95 antiangiogenesis drug…this sounds even more promising. Things like this make me more happy!

    1. Hmm. I think this design is more akin to using a laser beam in lieu of the shotgun, David.
      It only became capable as we learned more about the biology and biophysics of the situation; one can only hope it gets better with more knowledge.

      Thanks for the comment.

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    1. The bottom line…
      I have rarely found a drug development- that worked- that didn’t have a decent bottom line. Oh, it may not be the blockbuster one hoped, but, it certainly makes an operational profit.
      And, the supply- that depends upon how much profit is developed- or how much someone was able to invest to build the scale needed for the disease model.

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