@article{e43fd92907d6481aa1ecffddf05dbdd5,
title = "The tale of proteolysis targeting chimeras (PROTACs) for leucine-rich repeat kinase 2 (LRRK2)",
abstract = "Here we present the rational design and the synthetic methodologies towards proteolysis targeting chimeras (PROTACs) for the recently-emerged Parkinson's target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective and brain-penetrating kinase inhibitors were selected and their structure was appropriately modified to assemble a cereblon-targeting-PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells. However, data regarding the degradation of the target protein are inconclusive. The reasons for the inefficient degradation of the target are further discussed.",
keywords = "LRRK2, Cereblon, PROTAC, degradation, Parkinson's disease",
author = "Markella Konstantinidou and Asmaa Oun and Pragya Pathak and Bidong Zhang and Zefeng Wang and \{ter Brake\}, Frans and Amalia Dolga and Arjan Kortholt and Alexander Doemling",
note = "Funding Information: This research has been supported (to A.D.) through ITN “Accelerated Early stage drug dIScovery” (AEGIS, grant agreement no. 675555). Moreover, funding was received from the National Institutes of Health (2R01 GM097082‐05), the European Lead Factory (IMI; grant agreement no. 115489), the Qatar National Research Foundation (NPRP6‐065‐3‐012). and, COFUNDs ALERT (grant agreement no. 665250) and Prominent (grant agreement no. 754425) and KWF Kankerbestrijding grant (grant agreement no. 10504). A.M.D. is the recipient of a Stichting Parkinson Fonds (SPF) grant and a Rosalind Franklin Fellowship co‐funded by the European Union and the University of Groningen. A.K. is holder of a TUBITAK 2232 scholarship and additional funding was received from The Michael J. Fox Foundation for Parkinson's Research. Publisher Copyright: {\textcopyright} 2020 The Authors. ChemMedChem published by Wiley-VCH GmbH",
year = "2021",
month = mar,
day = "18",
doi = "10.1002/cmdc.202000872",
language = "English",
volume = "16",
pages = "959--965",
journal = "ChemMedChem",
issn = "1860-7179",
publisher = "WILEY-V C H VERLAG GMBH",
number = "6",
}