Saturday, July 16, 2011

Osteoporitic Mice in Space

Clinical trials will have one last hurrah on the Final Frontier: According to a July 5 press release from Amgen and UCB Pharma, the last flight of the space shuttle program (STS-135 on Shuttle Atlantis) will carry mice receiving a sclerostin antibody to counter bone density loss. Mild osteoporosis (bone loss) and muscle atrophy are nothing new to astronauts (or cosmonauts, taikonauts, etc.), whose bodies change due to lack of normal gravity and from "skeletal disuse" brought on by insufficient exercise in spacecraft - you can't easily jog a mile when your track is 122.17 feet long.

I hadn't heard about UCB Pharma until this press release, although it's surprising, given that they have nearly 9,000 people across 40 countries! UCB proudly proclaims three (3) core products: Cimzia (certolizumab), Vimpat (lacosamide), and Neupro (rotigotine). Cimzia, an anti-inflammatory monoclonal antibody, comes with a catch: it's marketed in Europe for rheumatoid arthritis, but in the US, it's exclusively marketed for Crohn's, a bowel disorder. The other two are more "small-molecule" (and thus up my alley).  Lacosamide is a simple benzyl- and acetyl-protected O-methylserine used to treat epileptic and neuropathic pain. Hmm....a small peptide affecting the brain...wonder if it'll be Scheduled?  You betcha.

Rotigotine, a chiral (S-enantiomer) tetrahydronaphthylphenol with a stapled-on thiophenylamine, has been approved for Parkinson's and RLS.  Its story is equally convoluted: the molecule was originally developed by Aderis Pharma, which used to be Discovery Pharma. As Aderis, it was acquired by Schwarz pharma in 2005, and Schwarz as a whole acquired by UCB a few years later.  Got that?  Four companies, one molecule, roughly twelve years. 

Aside from these products, UCB's cash cow is Keppra (levetiracetam, for neropathic pain) and several generics, among them Zyrtec (allergies) and omeprazole (heartburn and GERD).  Their total haul for all meds? 2.8 billion Euros / year in net sales.

Update (July 30, 7:25PM) - Phew! Commenter gippgig spurs me to make some (important) changes to the (previously incorrect) drug structures. I've also changed the description of lacosamide from "homoserine" to "O-methylserine."


  1. Hey! Congrats on the new digs!!! Glad that you've got your own space. Can't wait to read more!


  2. Lacosamide seems to be missing an O, and I'd call it a protected O-methylserine amide rather than homoserine (which is 2-amino-4-hydroxybutanoic acid).
    Isn't the rotigotine structure the S enantiomer?

  3. You changed both the text AND the structure so now the text says S but the structure shown is R!

  4. @gippgig - Nah, it's S. Check out Aldrich:

  5. If you follow the rules for assigning R or S designation you'll find that the structure as drawn is R: The highest priority is the N, the next highest is the C attached directly to the phenyl (C; HHC; CCC), then the C attached to the methylene (C; HHC; HHC), & then the H. Going from the N to the benzylic C to the other C is counterclockwise but with the H sticking out rather than going in that reverses everything so counterclockwise is R. Aldrich got it wrong but Tocris got it right:

  6. @gippgig: Agreed. Thanks again. I'll have to email Aldrich to have them correct it.