PF-06454589 is an analog of PF-06447475 which is a highly potent, brain penetrant and selective LRRK2 inhibitor which has been profiled in in vivo safety and pharmacodynamic studies. Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). The most common LRRK2 mutation, G2019S, which is relatively rare in the total population, gives rise to increased kinase activity. As such, LRRK2 kinase inhibitors are potentially useful in the treatment of PD.

Physicochemical Properties

Molecular Formula	C14H16N6O
Molecular Weight	284.32
Exact Mass	284.138
CAS #	1527473-30-8
Related CAS #	1527473-30-8
PubChem CID	72706837
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	582.0±50.0 °C at 760 mmHg
Flash Point	305.8±30.1 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.760
LogP	0.08
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	21
Complexity	363
Defined Atom Stereocenter Count	0
InChi Key	VNWKCLDQBNSJJO-UHFFFAOYSA-N
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)
Chemical Name	4-[5-(1-methylpyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine
Synonyms	PF-06454589; PF 06454589; PF06454589
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	In vitro activity: Kinase Assay: Cell Assay:
ln Vivo
Animal Protocol
References	:J Med Chem.2015 Jan 8;58(1):419-32.

Solubility Data

Solubility (In Vitro)

DMSO: 10 mM Water:N/A Ethanol:N/A

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. 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. 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 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	3.5172 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.