One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug
Apstrakt
Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MID design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the... treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.
Izvor:
Frontiers in Neuroscience, 2016, 10Izdavač:
- Frontiers Media Sa, Lausanne
Finansiranje / projekti:
- EU COST Action CM 1103
DOI: 10.3389/fnins.2016.00177
ISSN: 1662-453X
PubMed: 27199640
WoS: 000374817000002
Scopus: 2-s2.0-84966377266
Institucija/grupa
PharmacyTY - JOUR AU - Hughes, Rebecca E. AU - Nikolić, Katarina AU - Ramsay, Rona R. PY - 2016 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2592 AB - Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MID design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic. PB - Frontiers Media Sa, Lausanne T2 - Frontiers in Neuroscience T1 - One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug VL - 10 DO - 10.3389/fnins.2016.00177 ER -
@article{ author = "Hughes, Rebecca E. and Nikolić, Katarina and Ramsay, Rona R.", year = "2016", abstract = "Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MID design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.", publisher = "Frontiers Media Sa, Lausanne", journal = "Frontiers in Neuroscience", title = "One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug", volume = "10", doi = "10.3389/fnins.2016.00177" }
Hughes, R. E., Nikolić, K.,& Ramsay, R. R.. (2016). One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug. in Frontiers in Neuroscience Frontiers Media Sa, Lausanne., 10. https://doi.org/10.3389/fnins.2016.00177
Hughes RE, Nikolić K, Ramsay RR. One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug. in Frontiers in Neuroscience. 2016;10. doi:10.3389/fnins.2016.00177 .
Hughes, Rebecca E., Nikolić, Katarina, Ramsay, Rona R., "One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug" in Frontiers in Neuroscience, 10 (2016), https://doi.org/10.3389/fnins.2016.00177 . .