The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2).
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ABSTRACT:
SUBMITTER: Konstantinidou M
PROVIDER: S-EPMC8048960 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2).
Konstantinidou Markella M Oun Asmaa A Pathak Pragya P Zhang Bidong B Wang Zefeng Z Ter Brake Frans F Dolga Amalia M AM Kortholt Arjan A Dömling Alexander A
ChemMedChem 20201229 6
Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, 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 degradati ...[more]
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