Journal
ACS CHEMICAL NEUROSCIENCE
Volume 11, Issue 13, Pages 1871-1886Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.0c00176
Keywords
kinase; neurodegeneration; CNS; Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; KCGS; GWAS; SNP; IDG; SGC; iPSCs
Funding
- AbbVie [1097737]
- Bayer Pharma AG
- Boehringer Ingelheim
- Canada Foundation for Innovation
- Eshelman Institute for Innovation
- Genome Canada
- Genentech
- Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD] [115766]
- Janssen
- Merck KGaA Darmstadt Germany
- MSD
- Novartis Pharma AG
- Ontario Ministry of Economic Development and Innovation
- Pfizer
- Sao Paulo Research Foundation-FAPESP [2013/50724-5]
- Takeda
- Wellcome [106169/ZZ14/Z]
- ALSA Investigator Initiated Starter Grant [wa1127, U54AG065187]
- Ghislaine and Sebastian Van Berkom foundation
- McGill Healthy Brains for Healthy Lives
- [U24DK116204]
Ask authors/readers for more resources
Kinases are highly tractable drug targets that have reached unparalleled success in fields such as cancer but whose potential has not yet been realized in neuroscience. There are currently 55 approved small molecule kinase-targeting drugs, 48 of which have an anticancer indication. The intrinsic complexity linked to central nervous system (CNS) drug development and a lack of validated targets has hindered progress in developing kinase inhibitors for CNS disorders when compared to other therapeutic areas such as oncolo Identification and/or characterization of new kinases as potential drug targets for neurodegenerative diseases will create opportunities for the development of CNS drugs in the future. The track record of kinase inhibitors in other disease indications supports the idea that with the best targets identified small molecule kinase modulators will become impactful therapeutics for neurodegenerative diseases. This Review highlights the imminent need for new therapeutics to treat the most prevalent neurodegenerative diseases as well as the promise of kinase inhibitors to address this need. With a focus on kinases that remain largely unexplored after decades of dedicated research in the kinase field, we offer specific examples of understudied kinases that are supported by patient-derived data as linked to Alzheimer's disease, Parkinson's disease, and/or amyotrophic lateral sclerosis. Finally, we show literature-reported high-quality inhibitors for several understudied kinases and suggest other kinases that merit additional medicinal chemistry efforts to elucidate their therapeutic potential.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available