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Title

Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold: Potential pro-neurogenic agents

AuthorsSalado, Irene G. ; Zaldívar-Díez, Josefa; Sebastián-Pérez, Víctor; Li, Lingling; Geiger, Larissa; González, Silvia; Campillo, Nuria E. ; Gil, Carmen ; Morales, Aixa V. ; Pérez, Daniel I.; Martínez, Ana
KeywordsLRRK2 inhibitors
Protein kinase inhibitors
Indolinone
Adult neurogenesis
Neural stem cell
Regenerative medicine
Issue Date29-Sep-2017
PublisherElsevier
CitationEuropean Journal of Medicinal Chemistry 138: 328–342 (2017)
AbstractLeucine-rich repeat kinase 2 (LRRK2) is one of the most pursued targets for Parkinson’s disease (PD) therapy. Moreover, it has recently described its role in regulating Wnt signaling and thus, it may be involved in adult neurogenesis. This new hypothesis could give rise to double disease-modifying agents firstly by the benefits of inhibiting LRRK2 and secondly by promoting adult neurogenesis. Herein we report, the design, synthesis, biological evaluation, SAR and potential binding mode of indolinelike LRRK2 inhibitors and their preliminary neurogenic effect in neural precursor cells isolated from adult mice ventricular-subventricular zone. These results open new therapeutic horizons for the use of LRRK2 inhibitors as neuroregenerative agents.Moreover, the indolinone derivatives here prepared, inhibitors of the kinase activity of LRRK2, may be considered as pharmacological probes to study the potential neuroregeneration of the damaged brain.
Description46 p.-7 fig.-1 tab.
Publisher version (URL)http://dx.doi.org/10.1016/j.ejmech.2017.06.060
URIhttp://hdl.handle.net/10261/152301
DOI10.1016/j.ejmech.2017.06.060
ISSN0223-5234
E-ISSN1768-3254
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