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PF-06447475

CAS No. : 1527473-33-1

MCE 国际站：PF-06447475

产品活性：PF-06447475是高效，选择性，能透过血脑屏障的 LRRK2 抑制剂，IC₅₀值为3 nM。

研究领域：Autophagy

作用靶点：LRRK2

In Vitro: PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay with IC₅₀s of 3 and 25 nM, respectively. Cells incubated with PF-06447475 alone (0.5, 1, 3 μM) or in the presence of ROT significantly reduces (S935)-LRRK2 kinase phosphorylation to control. PF-06447475 significantly preserves the nucleus morphology and ΔΨm of NLCs exposed to ROT compared to untreated and control. PF-475 significantly diminishes ROT-induced ROS generation to a similar extent to cells exposed to PF-475 alone.

In Vivo: In G2019S+ rats treated with PF-06447475, a significant reduction in microgliosis to levels found in wild-type rats could be observed. The proinflammatory marker MHC-II expressed on myeloid cells but not neurons also appears to be less abundant in confocal sections in G2019S+ rats treated with PF-06447475. PF-06447475 treatment in G2019S+ rats significantly lowers the number of CD68 cells recruited to the SNpc. PF-06447475 successfully blocks the enhanced neuroinflammation associated with G2019S-LRRK2 expression. Treatment of G2019S+ rats with PF-06447475 preserves TH expression in the dorsal striatum, consistent with drug attenuating neurodegeneration in the SNpc. PF-06447475 is well tolerated in rats.

相关产品：Bioactive Compound Library Plus  |  Kinase Inhibitor Library  |  CNS-Penetrant Compound Library  |  Autophagy Compound Library  |  Anti-Parkinson's Disease Compound Library  |  Neurodegenerative Disease-related Compound Library  |  Highly Selective Inhibitors Library  |  CZC-54252 hydrochloride  |  PFE-360  |  CZC-25146  |  LRRK2/NUAK1/TYK2-IN-1  |  LRRK2-IN-7  |  PF-06371900  |  XL01126  |  LRRK2 inhibitor 1  |  LRRK2-IN-3  |  PF-06454589  |  LRRK2-IN-4  |  IKK 16 hydrochloride  |  GNE0877  |  LRRK2-IN-1  |  PF-06455943  |  LRRK2-IN-5  |  Indazole  |  LRRK2-IN-8  |  JH-II-127  |  GSK2578215A  |  GSK2646264  |  GNE-9605  |  PF-06456384  |  GNE-7915  |  LRRK2-IN-2  |  MLi-2

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