Identifying Mechanism-of-Action Targets for Drugs and Probes
News Jul 06, 2012
Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to "de-orphanize" drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration-approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria.
The article is published online in PNAS and is free to access.
Studying Ebola-Host Cell Interaction Helps Find Targets for Antiviral DrugsNews
In some ways, the Ebola virus operates like a vampire; only after it is politely invited in to a host cell does it take up the task of destroying everything in its path. In a new study researchers seek to elucidate quantitatively the biomechanical mechanism of Ebola-host cell interaction, providing potential new targets for antiviral drug development.READ MORE
Susan Audino Joins CloudLIMS’ Scientific Advisory BoardNews
Dr. Susan Audino, Chair of the Cannabis Working Group at AOAC International, has joined the Scientific Advisory Board at CloudLIMS, which specialises in data management solutions for cannabis testing laboratories.READ MORE
Researchers Discover Key Link Between Mitochondria and Cocaine AddictionNews
Researchers were able to block response in mitochondria to cocaine.READ MORE
Comments | 0 ADD COMMENT
World Advanced Therapies & Regenerative Medicine Congress
May 16 - May 18, 2018