GNE-0877   Click here for help

GtoPdb Ligand ID: 9393

Synonyms: compound 11 [PMID: 24354345] | DNL-201 | DNL201 [2] | GNE0877
PDB Ligand
Compound class: Synthetic organic
Comment: GNE-0877 (renamed DNL201; Denali Therapeutics) is a potent and selective, brain penetrant small molecule inhibitor of LRRK2 (leucine-rich repeat kinase 2) [1-2], a kinase whose aberrant activation is identified in a subset of patients with Parkinson's disease. LRRK2 ihnibitors are being developed as potential disease-modifying agents as therapeutics for Parkinson's disease.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 91.45
Molecular weight 339.14
XLogP 2.18
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#CC(n1nc(c(c1)Nc1ncc(c(n1)NC)C(F)(F)F)C)(C)C
Isomeric SMILES N#CC(n1nc(c(c1)Nc1ncc(c(n1)NC)C(F)(F)F)C)(C)C
InChI InChI=1S/C14H16F3N7/c1-8-10(6-24(23-8)13(2,3)7-18)21-12-20-5-9(14(15,16)17)11(19-4)22-12/h5-6H,1-4H3,(H2,19,20,21,22)
InChI Key ZPPUMAMZIMPJGP-UHFFFAOYSA-N
References
1. Estrada AA, Chan BK, Baker-Glenn C, Beresford A, Burdick DJ, Chambers M, Chen H, Dominguez SL, Dotson J, Drummond J et al.. (2014)
Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors.
J Med Chem, 57 (3): 921-36. [PMID:24354345]
2. Jennings D, Huntwork-Rodriguez S, Henry AG, Sasaki JC, Meisner R, Diaz D, Solanoy H, Wang X, Negrou E, Bondar VV et al.. (2022)
Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson's disease.
Sci Transl Med, 14 (648): eabj2658. DOI: 10.1126/scitranslmed.abj2658 [PMID:35675433]