A LRRK2 kinase inhibitor
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PF-06447475

Item No. 18375

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
3-[4-(4-morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-benzonitrile
CAS Number
1527473-33-1
Molecular Formula
C17H15N5O
Formula Weight
305.3
Purity
≥98%
Formulation (Request formulation change)
A crystalline solid
Solubility(Learn about Variance in Solubility)
DMF: 5 mg/mlDMF:PBS (pH 7.2); (1:7): 0.12 mg/mlDMSO: 2 mg/ml
λmax
224, 294 nm
SMILES
N#CC1=CC(C2=CNC3=NC=NC(N4CCOCC4)=C32)=CC=C1
InChi Code
InChI=1S/C17H15N5O/c18-9-12-2-1-3-13(8-12)14-10-19-16-15(14)17(21-11-20-16)22-4-6-23-7-5-22/h1-3,8,10-11H,4-7H2,(H,19,20,21)
InChi Key
BHTWDJBVZQBRKP-UHFFFAOYSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    5 mg

    $39

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    10 mg

    $70

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    25 mg

    $126

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    50 mg

    $193

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    Product Description

    PF-06447475 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC50 = 3 nM).1 It also inhibits LRRK2 containing a glycine-to-serine substitution at position 2019 (LRRK2G2019S; IC50 = 11 nM). PF-06447475 inhibits LRRK2 autoactivation in cells (IC50 = 25 nM). It inhibits paraquat-induced locomotor deficits, decreases in survival, and increases in cranial homogenate levels of malondialdehyde (MDA) in D. melanogaster.2 PF-06447475 (30 mg/kg twice per day) increases the number of total and tyrosine hydroxylase-expressing neurons and decreases the number of inducible nitric oxide synthase-expressing neurons in rat substantia nigra pars compacta (SNPC) in a transgenic model of Lrrk2G2019S- and α-synuclein-induced model of Parkinson's disease.3 It reduces levels of macrophage infiltration in the ipsilateral SNPC in the same model at the same dose.

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Henderson, J.L., Kormos, B.L., Hayward, M.M., 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. 58(1), 419-432 (2015).

    2. Quintero-Espinosa, D.A., Jimenez-Del-Rio, M., and Velez-Pardo, C. LRRK2 kinase inhibitor PF-06447475 protects Drosophila melanogaster against paraquat-induced locomotor impairment, life span reduction, and oxidative stress. Neurochem. Res. 49(9), 2440-2452 (2024).

    3. Daher, J.P.L., Abdelmotilib, H.A., Hu, X., et al. Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration. J. Bio. Chem. 290(32), 19433-19444 (2015).