Thursday, March 25, 2010

Retropharmacology: From Drug to lead

Drug discovery is a lengthy, high risk and costly endeavor; many strategies exist to accelerate the development process to provide the highest quality of the candidate. The diminished interest in Natural products drug discovery as the industry embraced promising and exciting new technologies, particularly combinatorial chemistry, but these new technologies promise to fill drug development pipeline with small molecule candidates is unfulfilled. Learning from the past with the appropriate strategy for the future is essential to make a significant difference
Valerian (valeriana officinalis) has been used as a medicinal herb science at least the time of ancient Greece and Rome as a sedative, migraine treatment, pain reliever , insomnia and other disorders as an alternative to benzodiazepine drugs
Valerenic acid which is a major constituent of common valerian is a potent modulator of GABA-A receptors. Inorder to develop a broader understanding of structural requirements for GABA-A modulatory activity of valerenic acid Kopp s et al (chem med chem) synthesized several analogues, and found that some of the derivatives such as tetrazole (pic) are proved to be the most potent allosteric potentiators of GABA-induced ion currents, and its activity is exceeds the activity of valerenic acid and Diazepam

This reverse pharmacology approach, relates to reversing the routine ‘laboratory-to-clinic’ progress to ‘clinics-to-laboratories’(inspired by traditional medicine), can offer a smart strategy for new drug candidates

Thursday, March 4, 2010

Small molecules or biopharmaceuticals

The movement of big pharma into biologics (biopharmaceuticals) understandably has a direct effect on pharmaceutical landscape. Companies shows a diminishing portfolio revenue from small molecules drugs, primarily because of patent expiration on blockbuster drugs (small molecules) and also due to the reallocation of industry resources towards biologics.

Biologics represent one of the most promising frontiers in pharmacotherapy, USFDA approved more biologics in 2009, the figure include 19 new molecular entities (NMEs) and six novel biologics. In 2008 FDA approved 21 NMEs and 3 novel biologics. A substantial improvement in biologics approvels in 2009. (fig.1, Nature medicine,139,16,2010) and it is expected to take over from small molecule field in the coming years( fig 2, Nature reviews/drug discovery ), But their cost can be substantial, reaching $ 200,000 or more annually for treatment (Cerezyme) and the large molecules drugs are administered via injection – a less popular option with patients.

Biologics are gradually going to replace the traditional approach to drug design. Students need to understand industries changing need, if they plan on carriers in this area.