Figure 7.

XL01126 surpassed its warhead and negative PROTAC cis-XL01126 in inhibiting downstream signaling in G2019S LRRK2 MEFs. Representative Western blots of total LRRK2, LRRK2-pSer935, pRab10, Rab10 total, and tubulin levels following the treatment of G2019S LRRK2 MEFs with HG-10-102-01 (A), XL01126 (A, B), and cis-XL01126 (B) at the indicated concentrations for 4 h. The relative LRRK2 protein and pRab10 levels were obtained by quantifying the ratios of total LRRK2/tubulin or Rab10-pThr73/total Rab10, respectively, and the ratios were normalized to the DMSO-treated samples. The relative LRRK2 and pRab10 protein levels were plotted against the compound concentration and fitted against “nonlinear regression, one site-fit log IC₅₀” in GraphPad to obtain the DC₅₀ and EC₅₀ values. Data were obtained from two independent biological experiments.