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PF-06447475
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PF-06447475图片
CAS NO:1527473-33-1
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 305.33
Formula C17H15N5O
CAS No. 1527473-33-1
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 33 mg/mL
Water: <1 mg/mL
Ethanol: N/A
SMILES Code N#CC1=CC=CC(C2=CNC3=NC=NC(N4CCOCC4)=C32)=C1
Synonyms PF6447475; PF-06447475; PF-6447475; PF06447475; PF 6447475; PF 06447475
实验参考方法
In Vitro

In vitro activity: PF-06447475 is a novel, highly potent, selective and brain penetrable LRRK2 inhibitor with IC50 of 3 nM. Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay with IC50s of 3 and 25 nM, respectively.


Kinase Assay: PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay with IC50s of 3 and 25 nM, respectively.


Cell Assay: 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 has the potential for the treatment of PD. 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 VivoIn 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
Animal model G2019S+ rats
Formulation & Dosage 3 and 30 mg/kg PF-06447475 (p.o. b.i.d.)
References J Med Chem. 2015 Jan 8;58(1):419-32. Neurochem Res. 2016 Oct;41(10):2675-2692. Epub 2016 Jul 9; J Biol Chem. 2015 Aug 7;290(32):19433-44