Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold : Potential pro-neurogenic agents
Copyright © 2017 Elsevier Masson SAS. All rights reserved..
Leucine-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 indoline-like 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:138 |
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| Enthalten in: |
European journal of medicinal chemistry - 138(2017) vom: 29. Sept., Seite 328-342 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Salado, Irene G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.09.2017 Date Revised 24.10.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2017.06.060 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM273646494 |
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| 100 | 1 | |a Salado, Irene G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold |b Potential pro-neurogenic agents |
| 264 | 1 | |c 2017 | |
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| 500 | |a Date Revised 24.10.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Leucine-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 indoline-like 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adult neurogenesis | |
| 650 | 4 | |a Indolinone | |
| 650 | 4 | |a LRRK2 inhibitors | |
| 650 | 4 | |a Neural stem cell | |
| 650 | 4 | |a Protein kinase inhibitors | |
| 650 | 4 | |a Regenerative medicine | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Neuroprotective Agents |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a indoline |2 NLM | |
| 650 | 7 | |a 6DPT9AB2NK |2 NLM | |
| 650 | 7 | |a LRRK2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Zaldivar-Diez, Josefa |e verfasserin |4 aut | |
| 700 | 1 | |a Sebastián-Pérez, Víctor |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lingling |e verfasserin |4 aut | |
| 700 | 1 | |a Geiger, Larissa |e verfasserin |4 aut | |
| 700 | 1 | |a González, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Campillo, Nuria E |e verfasserin |4 aut | |
| 700 | 1 | |a Gil, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Morales, Aixa V |e verfasserin |4 aut | |
| 700 | 1 | |a Perez, Daniel I |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Ana |e verfasserin |4 aut | |
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