Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H16F3N7 |
Molecular Weight | 339.3189 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNC1=NC(NC2=CN(N=C2C)C(C)(C)C#N)=NC=C1C(F)(F)F
InChI
InChIKey=ZPPUMAMZIMPJGP-UHFFFAOYSA-N
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)
GNE0877, aminopyrazole derivative, is a highly potent, selective, brain-penetrable LRRK2 inhibitor and an investigational drug for Parkinson's disease therapy. It inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation with an IC50 value of 3 nM in vivo. GNE0877 demonstrated metabolic stability, good oral bioavailability (88%) and brain penetration across multiple species.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24354345
Curator's Comment: Known to be CNS penetrant in mouse; rats; monkey. Human data not available
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q5S007 Gene ID: 120892.0 Gene Symbol: LRRK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24354345 |
0.7 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24354345
BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation were treated with GNE0877 10 and 50 mg/kg at 1, 3, and 6 h (n = 3/dose)
Route of Administration:
Intraperitoneal
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24354345
GNE-0877 showed significantly enhanced LRRK2 cellular potency (3 nM) and low turnover in human liver microsomes and hepatocytes with no evidence of glucuronidation.
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ANGHS285FG
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1374828-69-9
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ACTIVE MOIETY