PF-06447475
Based on 7 publication(s) in Google Scholar
PF-06447475 is a highly potent, selective and brain penetrant LRRK2 inhibitor with an IC50 of 3 nM.
For research use only. We do not sell to patients.
- Purity: 99.94%
- CAS No.: 1527473-33-1
- Formula: C17H15N5O
- Molecular Weight:305.33
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) PF-06447475
More- Autophagy. 2025 Aug 28:1-15. [Abstract]
- Antioxidants (Basel). 2022 Aug 23;11(9):1634. [Abstract]
- Cells. 2023 Mar 29;12(7):1040. [Abstract]
- Int Immunopharmacol. 2026 Apr 15:175:116414. [Abstract]
- iScience. 2024 Sep 16;27(10):110980. [Abstract]
- bioRxiv. 2025 Oct 12.
- Methods Mol Biol. 2021:2322:63-72. [Abstract]
Biological Activity
IC50: 3 nM (LRRK2)[1].
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
25 nM
Compound: 14
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Inhibition of full length LRRK2 (unknown origin) expressed in HEK293 cells assessed as reduction in S935 phosphorylation incubated for 90 mins by ELISA method
Inhibition of full length LRRK2 (unknown origin) expressed in HEK293 cells assessed as reduction in S935 phosphorylation incubated for 90 mins by ELISA method
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[PMID: 25353650] |
PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay with IC50s of 3 and 25 nM, respectively[1]. 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[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 1527473-33-1
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Appearance Solid
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Molecular Weight 305.33
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Formula C17H15N5O
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Color Off-white to pink
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SMILES
N#CC1=CC=CC(C2=CNC3=NC=NC(N4CCOCC4)=C32)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (7)
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Journal Impact Factor
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Most Recent
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Autophagy
2025 Aug 28:1-15. PMID: 40851277 -
Antioxidants (Basel)
LRRK2 Inhibition by PF06447475 Antagonist Modulates Early Neuronal Damage after Spinal Cord Trauma. [Abstract]2022 Aug 23;11(9):1634. PMID: 36139708 -
Cells
Inhibition of LRRK2 Attenuates Depression-Related Symptoms in Mice with Moderate Traumatic Brain Injury. [Abstract]2023 Mar 29;12(7):1040. PMID: 37048114 -
Int Immunopharmacol
Inhibition of LRRK2 alleviates LPS-induced hippocampal pericyte loss and depressive-like behaviors through suppressing the RIPK1-mediated necroptosis pathway. [Abstract]2026 Apr 15:175:116414. PMID: 41740343 -
iScience
Rebalance of mitophagy by inhibiting LRRK2 improves colon alterations in an MPTP in vivo model. [Abstract]2024 Sep 16;27(10):110980. PMID: 39635134 -
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Methods Mol Biol
Two Methods to Analyze LRRK2 Functions Under Lysosomal Stress: The Measurements of Cathepsin Release and Lysosomal Enlargement. [Abstract]2021:2322:63-72. PMID: 34043193
Solvent & Solubility
DMSO : 60 mg/mL (196.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 3 mg/mL (9.83 mM); Clear solution
This protocol yields a clear solution of ≥ 3 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (30.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Rats: PF-06447475 are administered to the desired amount in a suspension solution consisting of 10% propylene glycol, 20% PEG-400, and 70% 0.5% methylcellulose. To determine the potency of PF-06447475 in blocking brain LRRK2 kinase activity, wild-type Sprague-Dawley rats are treated at 3 and 30 mg/kg PF-06447475 (p.o. b.i.d.) for 14 days, and total and phospho-LRRK2 are subsequently measured from brain tissue lysates[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (283 KB)
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SDS (419 KB)
- English - EN (419 KB)
- Français - FR (419 KB)
- Deutsch - DE (419 KB)
- Norwegian - NO (419 KB)
- Español - ES (419 KB)
- Swedish - SV (419 KB)
- Italian - IT (419 KB)
- Korean - KR (419 KB)
- Portuguese - PT (419 KB)
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Handling Instructions (2659 KB)
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. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.2751 mL | 16.3757 mL | 32.7515 mL | 81.8786 mL |
| 5 mM | 0.6550 mL | 3.2751 mL | 6.5503 mL | 16.3757 mL | |
| 10 mM | 0.3275 mL | 1.6376 mL | 3.2751 mL | 8.1879 mL | |
| 15 mM | 0.2183 mL | 1.0917 mL | 2.1834 mL | 5.4586 mL | |
| 20 mM | 0.1638 mL | 0.8188 mL | 1.6376 mL | 4.0939 mL | |
| 25 mM | 0.1310 mL | 0.6550 mL | 1.3101 mL | 3.2751 mL | |
| 30 mM | 0.1092 mL | 0.5459 mL | 1.0917 mL | 2.7293 mL | |
| 40 mM | 0.0819 mL | 0.4094 mL | 0.8188 mL | 2.0470 mL | |
| 50 mM | 0.0655 mL | 0.3275 mL | 0.6550 mL | 1.6376 mL | |
| 60 mM | 0.0546 mL | 0.2729 mL | 0.5459 mL | 1.3646 mL | |
| 80 mM | 0.0409 mL | 0.2047 mL | 0.4094 mL | 1.0235 mL | |
| 100 mM | 0.0328 mL | 0.1638 mL | 0.3275 mL | 0.8188 mL |
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