| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PF-06454589 targets leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein kinase that is a major genetic contributor to Parkinson's disease. By acting as a potent and selective inhibitor of LRRK2, it blocks the kinase activity of the enzyme, preventing the phosphorylation of its downstream substrates. This inhibition is thought to modulate cellular pathways involved in neurodegeneration.
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| ln Vitro |
In vitro, PF-06454589 is a potent and selective LRRK2 inhibitor. It inhibits LRRK2 kinase activity with high potency. The compound demonstrates selectivity for LRRK2 over other kinases. However, specific IC₅₀ values for PF-06454589 are not detailed in the available literature, though related compounds show IC₅₀ values in the low nanomolar range.
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| ln Vivo |
In vivo, PF-06454589 has the potential to modulate LRRK2 activity in the brain. As a potent and selective LRRK2 inhibitor, it may have therapeutic potential for Parkinson's disease and other neurodegenerative disorders. However, specific in vivo efficacy data in animal models are not extensively detailed in the available literature.
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| Enzyme Assay |
In vitro LRRK2 kinase assays for PF-06454589 are performed using purified recombinant LRRK2 enzyme. The kinase is incubated with a peptide substrate and ATP in the presence of varying concentrations of PF-06454589. Phosphorylation is detected using a luminescence-based or fluorescence-based assay. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays for PF-06454589 are performed using cell lines expressing LRRK2. Cells are cultured in appropriate media and treated with PF-06454589 at various concentrations. LRRK2 phosphorylation and downstream signaling are assessed by Western blot. Cell viability is measured by MTT assays. The compound's effects on cellular pathways involved in neurodegeneration can also be assessed.
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| Animal Protocol |
In vivo animal studies for PF-06454589 would typically involve rodent models of Parkinson's disease, such as the MPTP or 6-OHDA models. The compound is administered orally or intraperitoneally. Motor function is assessed using behavioral tests. LRRK2 activity and phosphorylation of its substrates are measured in brain tissue. The compound's neuroprotective effects are evaluated histologically.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of PF-06454589, such as half-life and oral bioavailability, are not extensively detailed in the available literature. It is described as a brain-penetrant LRRK2 kinase inhibitor. It is soluble in DMSO at 10 mg/mL. The compound is stable as a powder and should be stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for PF-06454589 are not widely available in public literature. As a research compound, it is intended for laboratory use only and is not for human therapeutic use. Standard safety precautions should be followed when handling this compound. The compound is supplied with a purity of ≥98%.
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| References |
:J Med Chem.2015 Jan 8;58(1):419-32.
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| Additional Infomation |
PF-06454589 is a potent and selective LRRK2 inhibitor. It is also known as PF 06454589 and has a CAS number 1527473-30-8. It is a valuable research tool for studying the role of LRRK2 in Parkinson's disease and other neurodegenerative disorders. This product is for research use only.
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| Molecular Formula |
C14H16N6O
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| Molecular Weight |
284.32
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| Exact Mass |
284.138
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| CAS # |
1527473-30-8
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| Related CAS # |
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| PubChem CID |
72706837
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
582.0±50.0 °C at 760 mmHg
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| Flash Point |
305.8±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.760
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| LogP |
0.08
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
363
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VNWKCLDQBNSJJO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16N6O/c1-19-8-10(6-18-19)11-7-15-13-12(11)14(17-9-16-13)20-2-4-21-5-3-20/h6-9H,2-5H2,1H3,(H,15,16,17)
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (4.40 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 12.5 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: ≥ 1.25 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5172 mL | 17.5858 mL | 35.1716 mL | |
| 5 mM | 0.7034 mL | 3.5172 mL | 7.0343 mL | |
| 10 mM | 0.3517 mL | 1.7586 mL | 3.5172 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.
 J Med Chem.2015 Jan 8;58(1):419-32. |
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