LRRK2 and Parkinson disease: Very recently, the thioether linkage in VHL ligands has also been exploited by the Ciulli and Alessi laboratories in the development of Leucine Rich Repeat Kinase 2 (LRRK2) PROTAC degraders.126 LRRK2 is an attractive target for treating Parkinson's Disease, which has been associated with both increased LRRK2 activity and pathologic LRRK2 mutations.169,170 Starting from LRRK2 inhibitor HG-10-102-01 as LRRK2 binding moiety, a small set of PROTACs was designed to recruit cIAP, CRBN, or VHL, the latter connected either via the RHS phenolic or LHS thioether vector.