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Details

Stereochemistry ACHIRAL
Molecular Formula C24H18FN3O2
Molecular Weight 399.417
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GSK-2578215A

SMILES

FC1=NC=CC(=C1)C2=CC=C(OCC3=CC=CC=C3)C(=C2)C(=O)NC4=CC=CN=C4

InChI

InChIKey=WCIGMFCFPXZRMQ-UHFFFAOYSA-N
InChI=1S/C24H18FN3O2/c25-23-14-19(10-12-27-23)18-8-9-22(30-16-17-5-2-1-3-6-17)21(13-18)24(29)28-20-7-4-11-26-15-20/h1-15H,16H2,(H,28,29)

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26435084

GSK-2578215A is a potent and highly selective LRRK2 kinase inhibitor that possesses good blood-brain barrier (BBB) permeability with a high ratio of brain to plasma distribution in mice. GSK-2578215A was identified in a screen of GlaxoSmithKline’s KCS (a kinase-focused set of compounds for lead discovery) using a homogeneous time-resolved fluorescence (HTRF) assay that measured the inhibition of phosphorylation of the peptide substrate LRRKtide by baculoviral-derived recombinant 6His-Tev-LRRK2 (1326-2527). SAR and optimization of leads was performed using similar recombinant LRRK2 enzyme assays. GSK-2578215A exhibited biochemical IC50s of 10.9 and 8.9 nM against wild-type LRRK2 and LRRK2 [G2019S], respectively. The ability of GSK-2578215A to reduce phosphorylation levels of Ser910 and Ser935 in peripheral tissues on dosing to mice supports the notion that these phosphoepitopes can serve as markers of LRRK2 inhibitor activity in animal studies. Gene variants of the leucine-rich repeat kinase 2 (LRRK2) are associated with susceptibility to Parkinson's disease (PD). GSK-2578215A can be potentially used for the treatment of Parkinson's disease and other neurodegenerative diseases.

CNS Activity

Curator's Comment: good blood-brain barrier (BBB) permeability

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.9 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

In vivo, GSK-2578215A (100 mg/kg i.p.) inhibits Ser910 and Ser935 phosphorylation in mouse spleen and kidney.
Route of Administration: Intraperitoneal
GSK-2578215A exhibits exceptionally high selectivity for LRRK2 across the kinome, substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.3-1.0 uM in cells and in mouse spleen and kidney, but not in brain, following intraperitoneal injection of 100mg/kg.
Name Type Language
GSK-2578215A
Common Name English
BENZAMIDE, 5-(2-FLUORO-4-PYRIDINYL)-2-(PHENYLMETHOXY)-N-3-PYRIDINYL-
Preferred Name English
Code System Code Type Description
PUBCHEM
68107965
Created by admin on Mon Mar 31 22:05:13 GMT 2025 , Edited by admin on Mon Mar 31 22:05:13 GMT 2025
PRIMARY
CAS
1285515-21-0
Created by admin on Mon Mar 31 22:05:13 GMT 2025 , Edited by admin on Mon Mar 31 22:05:13 GMT 2025
PRIMARY
FDA UNII
Q641JSF42X
Created by admin on Mon Mar 31 22:05:13 GMT 2025 , Edited by admin on Mon Mar 31 22:05:13 GMT 2025
PRIMARY