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].
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
|
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] |