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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
Structure of GNE-0877

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)

HIDE SMILES / InChI

Molecular Formula C14H16F3N7
Molecular Weight 339.3189
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.7 nM [Ki]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors.
2014 Feb 13
Patents

Patents

Sample Use Guides

In Vivo Use Guide
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
GNE-0877 showed significantly enhanced LRRK2 cellular potency (3 nM) and low turnover in human liver microsomes and hepatocytes with no evidence of glucuronidation.
Substance Class Chemical
Created
by admin
on Tue Oct 22 13:08:37 UTC 2019
Edited
by admin
on Tue Oct 22 13:08:37 UTC 2019
Record UNII
ANGHS285FG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GNE-0877
Code English
1H-PYRAZOLE-1-ACETONITRILE, .ALPHA.,.ALPHA.,3-TRIMETHYL-4-((4-(METHYLAMINO)-5-(TRIFLUOROMETHYL)-2-PYRIMIDINYL)AMINO)-
Common Name English
Related Record Type Details
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TRANSPORTER -> NON-SUBSTRATE
METABOLIC ENZYME -> INDUCER
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
CSF/PLASMA RATIO PHARMACOKINETIC