title: Multitarget drug discovery projects in CNS diseases: quantitative systems pharmacology as a possible path forward.
abstract: Clinical development in brain diseases has one of the lowest success rates in the pharmaceutical industry, and many promising rationally designed single-target R&D projects fail in expensive Phase III trials. By contrast, successful older CNS drugs do have a rich pharmacology. This article will provide arguments suggesting that highly selective single-target drugs are not sufficiently powerful to restore complex neuronal circuit homeostasis. A rationally designed multitarget project can be derisked by dialing in an additional symptomatic treatment effect on top of a disease modification target. Alternatively, we expand upon a hypothetical workflow example using a humanized computer-based quantitative systems pharmacology platform. The hope is that incorporating rationally multipharmacology drug discovery could potentially lead to more impactful polypharmacy drugs.
authors.affiliation: In Silico Biosciences, PA, USA. hugo-geerts@in-silico-biosciences.com
authors.forename: Hugo
authors.initials: H
authors.lastname: Geerts
authors.forename: Ludo
authors.initials: L
authors.lastname: Kennis
mesh_terms: D002491:Central Nervous System Agents / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D055808:Drug Discovery; D006801:Humans; D064798:Polypharmacology; D049490:Systems Biology
chemical_list: D002491:Central Nervous System Agents