Terra Sigillata

[Retraction 14 December 2007: Following a consideration of comments by Prof Ian Musgrave (below), I must retract my recommendation of this table – upon re-examination, I should have been much more critical of the information provided.)

The Wall Street Journal online has a nice general information table comparing and contrasting small molecules vs. proteins used as drugs. Biotechnology products like insulin or erythropoeitin protein molecules whereas classic drugs like the statins or antiinflammatory drugs are termed “small molecules.” In truth, both classes are pharmaceuticals so I would’ve used different headers: many biotechnology products are indeed pharmaceuticals.

Being a business newspaper the Journal also links to the main players in each field although many companies develop both kinds of drugs.

A nice quick primer for the average Terra Sig reader.

Comments

  1. #1 cobbler
    December 12, 2007

    thanks for this. i always wondered how a biologic was different from other drugs.

  2. #2 Ian Musgrave
    December 14, 2007

    I’m going to respectfully disagree with you here Abel, there is nothing nice about it and it displays an astounding degree of ignorance.

    Chemical drugs are essentially made up of elements from the periodic table.

    Essentially! essentially! They are composed of elements of the periodic table, as are biologicals. The article makes it sound as if all small molecule drugs are built from raw atoms, and biologicals come from some ethereal plane, where organisms make things constructed from matter not of this world (is the carbon in insulin not from the periodic table, after all).

    Few small molecule drugs would be constructed de-novo from raw elements, more often they are made simpler building blocks that are multi-atom compounds to begin with, or modifications of naturally occurring products. Most of the statins are modifications of bacterial fermentation products (their example, Lipitor, atorvastatin, is made synthetically, with staring products that include the amino-acid valine, derived from fermentation).

    What’s wrong with saying that “pharmaceuticals” are small non-protein molecules, and that biologics are proteins or peptides (they may have to explain that, but it would be better than what they have got currently).

    Automatic molecule screening systems are used in both small molecule drugs and biologics.

    Because they’re not as targeted as biologic drugs, chemical medicines can come with more side effects.

    What!!!! The whole point of modern pharmacology is to develop highly targeted drugs (with recent exceptions of multi-target anti-cancer drugs). HMG-CoA reductase inhibitors (for example) are just as targeted as biologicals and have few side effects (most of those due to its effect on the target). Vioxx, which was withdrawn because of side effects, had those side effects because it was a highly targeted drug. The biological erythropoeitin has a wide range of side effects, with some really nasty ones.

    All in all, although it has a few good points, the severe misrepresentation of the small molecule and biological drugs it produces outweighs the benefits.

    The rant endeth here.

  3. #3 Abel Pharmboy
    December 14, 2007

    Guilty as charged, Prof Musgrave. After re-reading the table along side your comments, I see the error of my ways and also must retract my support for this information source. I would even go farther back to note that methotrexate was also an early targeted drug, designed to resemble folate to inhibit dihydrofolate reductase. And, yes, the thing about the elements is terribly simplistic and wrong. We are learning that many biologics are no more selective than small molecules – witness the cardiotoxicity of Herceptin.

  4. #4 Ian Musgrave
    December 15, 2007

    Yeah, I was going to point out the Herceptin thing as well (but it looks like lowering the concentration and using it for a shorter time is just as effective and reduces the cardiotoxicity). Biologics do things we just can’t get small molecules to do. We have not successfully made a small molecule mimic of insulin, and many of the large peptide hormones will never be duplicated by small molecules (now that I’ve said that, someone will prove me wrong next week, just watch). But any drug that has a physiological effect will have side effects, no matter what.

    There is a range of oddness in the WSJ article (flasks or perti dishes? Try 1,000- 10,000 litre fermentation vats, microcentrifuges?? In someone research lab maybe, but not Pharmaceutical grade production), but it is only apparent after the element double take. Maybe we so so used to journalists getting things appallingly wrong that something that looks superficially okay is such a breath of fresh air the flaws are overlooked.

    Anyway, don’t worry too much, at least the WSJ was trying to make sense of things, many paers don’t even do that.

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