| CAS NO: | 1527473-33-1 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 询价 |
| 10mg | 询价 |
| 25mg | 询价 |
| 50mg | 询价 |
| 100mg | 询价 |
| 250mg | 询价 |
| 500mg | 询价 |
| 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 |
| 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 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 |
| 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 |
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