To scope and assess the degradation activity of XL01126 on other LRRK2 mutants and cell lines, dose-dependent degradation assays of XL01126 were carried out in R1441C LRRK2 MEFs (Figure ), bone marrow-derived macrophages (BMDMs), and human peripheral blood mononuclear cells (PBMCs) (Figure ). XL01126 exhibited potent LRRK2 degradation in all these cell types, with significant differentiation observed between XL01126 and cis-XL01126 in terms of Rab10 dephosphorylation (Table , Figure , and Figure ). The fast (T1/2, 300 nM = 2.4h) and potent (DC50, 4h = 72 nM, DC50, 24h = 17 nM) degradation of human LRRK2 in PBMCs suggests the potential of applying XL01126 to additional human cell lines. Testing of XL01126 and cis-XL01126 on SH-SY5Y, a human neuroblastoma cell line widely used as PD cell model , revealed that XL01126 induced 50% or more degradation of LRRK2 after 6h/300 nM or 24h/300 nM treatment (Figure ).