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.
Joint Lab on Artificial Intelligence and Computer Vision EstablishedNews
The Hong Kong University of Science and Technology signed a Memorandum of Understanding with Megvii (Face++) yesterday on establishing a joint laboratory on artificial intelligence (AI) and computer vision. The lab will be dedicated to improving people’s living and advance knowledge frontiers.READ MORE
First Successful Gene Therapy Trial Reported for People with Hemophilia ANews
Patients with hemophilia A who received a single infusion of an investigational gene therapy showed improved levels of the essential blood clotting protein FVIII, with 11 of 13 achieving normal or near-normal FVIII levels.READ MORE
Some Immune Cells May Help Tumors Instead of Destroying ThemNews
New data shows that neutrophils promote tumor progression and can actually hamper the work of immunotherapy in lung cancer.READ MORE