PF-06447475   Click here for help

GtoPdb Ligand ID: 8054

PDB Ligand
Compound class: Synthetic organic
Comment: PF-06447475 was reported as a potent, brain-pentrant inhibitor of the serine-threonine kinase, leucine-rich repeat kinase 2 (LRRK2) [2]. The compound's pharmacokinetic properties halted its progress towards clinical development, but it is a useful tool for the investigation of central and peripheral LRRK2 function in experimental models of Parkinson's disease for example [1,3-5].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 77.83
Molecular weight 305.13
XLogP 2.85
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#Cc1cccc(c1)c1c[nH]c2c1c(ncn2)N1CCOCC1
Isomeric SMILES N#Cc1cccc(c1)c1c[nH]c2c1c(ncn2)N1CCOCC1
InChI 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
References
1. Giraldo-Berrio D, Mendivil-Perez M, Velez-Pardo C, Jimenez-Del-Rio M. (2024)
Rotenone Induces a Neuropathological Phenotype in Cholinergic-like Neurons Resembling Parkinson's Disease Dementia (PDD).
Neurotox Res, 42 (3): 28. [PMID:38842585]
2. Henderson JL, Kormos BL, Hayward MM, Coffman KJ, Jasti J, Kurumbail RG, Wager TT, Verhoest PR, Noell GS, Chen Y et al.. (2015)
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): 419-32. [PMID:25353650]
3. Kania E, Long JS, McEwan DG, Welkenhuyzen K, La Rovere R, Luyten T, Halpin J, Lobbestael E, Baekelandt V, Bultynck G et al.. (2023)
LRRK2 phosphorylation status and kinase activity regulate (macro)autophagy in a Rab8a/Rab10-dependent manner.
Cell Death Dis, 14 (7): 436. [PMID:37454104]
4. Mutti V, Carini G, Filippini A, Castrezzati S, Giugno L, Gennarelli M, Russo I. (2023)
LRRK2 Kinase Inhibition Attenuates Neuroinflammation and Cytotoxicity in Animal Models of Alzheimer's and Parkinson's Disease-Related Neuroinflammation.
Cells, 12 (13). [PMID:37443833]
5. Quintero-Espinosa DA, Jimenez-Del-Rio M, Velez-Pardo C. (2024)
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. [PMID:38847910]