PF-06447475 is a highly potent, selective, brain penetrant LRRK2 inhibitor with IC0 of 3 nM/11 nM for Wt LRRK2/G2019S LRRK2 respectively. PF-06447475 was sufficiently potent in the LRRK2 whole cell assay (WCA; IC50=25 nM) (pS935 end point) to warrant additional profiling. Oral administration of PF-06447475 twice daily for 15 days was well tolerated at doses up to 60 mg kg-1 day-1 (31-fold Cave,0.24h; 70-fold Cmax) with only minimal alterations in RBC parameters, electrolytes, and food consumption without concurrent effects on body weight.
Cell Experiment | |
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Cell lines | |
Preparation method | |
Concentrations | |
Incubation time |
Animal Experiment | |
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Animal models | G2019S BAC-transgenic mice |
Formulation | 10% propylene glycol/20% PEG400/70% 9.5% methocellulose |
Dosages | 100 mg/kg |
Administration | p.o. |
Molecular Weight | 305.33 |
Formula | C17H15N5O |
CAS Number | 1527473-33-1 |
Solubility (25°C) | DMSO 30 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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