Replies to post #141402 on Biotech Values

[ariadndndough]

dew. correct me if i am wrong, but mrk drug is much more potent then roche's correct. and may act differently???

i thought i remember that from mrk's analyst day?

[biotech jim]

The Roche result with dalcetrapib was expected (by me at least). The problem(s) in part lies within this abstract by MRK. Who can pinpoint the problem(s)? My view is that drug discoverers/developers and astute investors will not see this is not a class issue, so other developers can be a buy on any such related stock weakness. Roche problems with efficacy (??) as well as my view re the other issue(s), they should know better.

http://www.ncbi.nlm.nih.gov/pubmed/20458119

J Lipid Res. 2010 Sep;51(9):2739-52. Epub 2010 May 10.
Biochemical characterization of cholesteryl ester transfer protein inhibitors.
Ranalletta M, Bierilo KK, Chen Y, Milot D, Chen Q, Tung E, Houde C, Elowe NH, Garcia-Calvo M, Porter G, Eveland S, Frantz-Wattley B, Kavana M, Addona G, Sinclair P, Sparrow C, O'Neill EA, Koblan KS, Sitlani A, Hubbard B, Fisher TS.
SourceMerck Research Laboratories, Rahway, NJ 07065, USA.

Abstract
Cholesteryl ester transfer protein (CETP) has been identified as a novel target for increasing HDL cholesterol levels. In this report, we describe the biochemical characterization of anacetrapib, a potent inhibitor of CETP. To better understand the mechanism by which anacetrapib inhibits CETP activity, its biochemical properties were compared with CETP inhibitors from distinct structural classes, including torcetrapib and dalcetrapib. Anacetrapib and torcetrapib inhibited CETP-mediated cholesteryl ester and triglyceride transfer with similar potencies, whereas dalcetrapib was a significantly less potent inhibitor. Inhibition of CETP by both anacetrapib and torcetrapib was not time dependent, whereas the potency of dalcetrapib significantly increased with extended preincubation. Anacetrapib, torcetrapib, and dalcetrapib compete with one another for binding CETP; however anacetrapib binds reversibly and dalcetrapib covalently to CETP. In addition, dalcetrapib was found to covalently label both human and mouse plasma proteins. Each CETP inhibitor induced tight binding of CETP to HDL, indicating that these inhibitors promote the formation of a complex between CETP and HDL, resulting in inhibition of CETP activity.

(Free pdf upon clicking the abstract link...)