| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
PF-06447475 (PF06447475) is a novel, highly potent, selective and brain penetrable inhibitor of Leucine rich repeat kinase 2 (LRRK2) with anti-PD activity. It inhibits LRRK2 with IC50 of 3 nM. 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. 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.
| ln Vitro |
With IC50s of 3 and 25 nM, respectively, PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay[1]. Cells treated with PF-06447475 alone (0.5, 1, 3 μM) or with ROT significantly lower the phosphorylation of (S935)-LRRK2 kinase compared to control. Compared to untreated and control, PF-06447475 significantly preserves the nucleus morphology and ΔΨm of NLCs exposed to ROT. PF-475 considerably reduces ROS production induced by ROT to a level comparable to cells exposed to PF-475 alone[2].
|
||
|---|---|---|---|
| ln Vivo |
Microgliosis in G2019S+ rats treated with PF-06447475 was significantly reduced to levels observed in wild-type rats. In confocal sections, the proinflammatory marker MHC-II, which is expressed on myeloid cells but not neurons, also seems to be less prevalent in G2019S+ rats given PF-06447475. In G2019S+ rats, treatment with PF-06447475 dramatically reduces the amount of CD68 cells recruited to the SNpc. PF-06447475 effectively inhibits the increased neuroinflammation linked to the expression of G2019S-LRRK2. TH expression in the dorsal striatum, which is in line with medication that lessens SNpc neurodegeneration[3]. Rats are able to tolerate PF-06447475 well[1].
|
||
| Animal Protocol |
|
||
| References |
[1]. Henderson JL, et al. Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor. J Med Chem. 2015 Jan 8;58(1):419-32.
[2]. Mendivil-Perez M, et al. Neuroprotective Effect of the LRRK2 Kinase Inhibitor PF-06447475 in Human Nerve-Like Differentiated Cells Exposed to Oxidative Stress Stimuli: Implications for Parkinson's Disease. Neurochem Res. 2016 Oct;41(10):2675-2692. [3]. Daher JP, et al. Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration. J Biol Chem. 2015 Aug 7;290(32):19433-44 |
| Molecular Formula |
C17H15N5O
|
|
|---|---|---|
| Molecular Weight |
305.33
|
|
| CAS # |
1527473-33-1
|
|
| Related CAS # |
|
|
| SMILES |
N#CC1=CC=CC(C2=CNC3=NC=NC(N4CCOCC4)=C32)=C1
|
|
| Synonyms |
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2751 mL | 16.3757 mL | 32.7514 mL | |
| 5 mM | 0.6550 mL | 3.2751 mL | 6.5503 mL | |
| 10 mM | 0.3275 mL | 1.6376 mL | 3.2751 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Efficacy and pharmacodynamic properties of the LRRK2 kinase inhibitor PF-06447475.J Biol Chem.2015 Aug 7;290(32):19433-44. |
|---|
 LRRK2 kinase inhibition is well tolerated in rats.J Biol Chem.2015 Aug 7;290(32):19433-44. |
 PF-06447475 administration blocks α-synuclein-induced dopaminergic neurodegeneration.J Biol Chem.2015 Aug 7;290(32):19433-44. |
 Microgliosis associated with G2019S-LRRK2 expression is attenuated by PF-06447475 in G2019S-LRRK2 rats.J Biol Chem.2015 Aug 7;290(32):19433-44. |
|---|
 Reduced CD68 cell recruitment in G2019S-LRRK2 rats treated with PF-06447475.J Biol Chem.2015 Aug 7;290(32):19433-44. |
 G2019S-LRRK2 expression enhances α-synuclein-induced dopaminergic neurodegeneration.J Biol Chem.2015 Aug 7;290(32):19433-44. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA