1374828-69-9 Usage
Description
GNE-0877 is a selective, brain-penetrable leucine-rich repeat kinase 2 (LRRK2) inhibitor with high potency (Ki = 0.7 nM). It is designed to target the LRRK2 enzyme, which is associated with the development of Parkinson's disease due to mutations that increase its kinase activity. GNE-0877 effectively inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing the G2019S Parkinson’s disease mutation, with an IC50 value of 3 nM in vivo.
Uses
Used in Pharmaceutical Industry:
GNE-0877 is used as a therapeutic agent for the treatment of Parkinson's disease. It targets the LRRK2 enzyme, which is linked to the disease's progression, and helps in reducing the increased kinase activity associated with the condition. By inhibiting LRRK2, GNE-0877 has the potential to protect dopaminergic cells from degeneration and slow down the progression of Parkinson's disease.
Used in Research and Development:
GNE-0877 is also used as a research tool for studying the role of LRRK2 in the pathogenesis of Parkinson's disease. Its high selectivity and potency make it a valuable compound for investigating the molecular mechanisms underlying the disease and for identifying potential therapeutic targets for future drug development.
in vitro
gne-0877 showed significantly enhanced lrrk2 cellular potency (3 nm) and low turnover in human liver microsomes and hepatocytes with no evidence of glucuronidation. invitrogen kinase-selectivity profiling (188 kinases) of gne-0877 at 0.1 μm resulted in only four kinases showing greater than 50% inhibition and suggested that gne-0877 is a highly selective lrrk2 inhibitor. furthermore, gne-0877 possessed a 212-fold biochemical-selectivity index over ttk (ki = 150 nm) [1].
in vivo
gne-0877 was evaluated for its ability to inhibit in vivo lrrk2 ser1292 autophosphorylation using bac transgenic mice expressing human lrrk2 protein with the g2019s parkinson’s disease mutation. using free-drug concentrations, robust concentration-dependent inhibition of ser1292 autophosphorylation was observed for gne-0877 [1].
references
[1] estrada aa, chan bk, baker-glenn c, beresford a, burdick dj, chambers m, chen h, dominguez sl, dotson j, drummond j, flagella m, fuji r, gill a, halladay j, harris sf, heffron tp, kleinheinz t, lee dw, le pichon ce, liu x, lyssikatos jp, medhurst ad, moffat jg, nash k, scearce-levie k, sheng z, shore dg, wong s, zhang s, zhang x, zhu h, sweeney zk. discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (lrrk2) small molecule inhibitors. j med chem. 2014 feb 13;57(3):921-36.
Check Digit Verification of cas no
The CAS Registry Mumber 1374828-69-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,7,4,8,2 and 8 respectively; the second part has 2 digits, 6 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1374828-69:
(9*1)+(8*3)+(7*7)+(6*4)+(5*8)+(4*2)+(3*8)+(2*6)+(1*9)=199
199 % 10 = 9
So 1374828-69-9 is a valid CAS Registry Number.
1374828-69-9Relevant articles and documents
PROCESS FOR THE PREPARATION OF PYRIMIDINYL-4-AMINOPYRAZOLE COMPOUNDS
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, (2019/07/13)
The present disclosure relates to methods of making LRRK2-inhibiting, pyrimidinyl-4-aminopyrazole compounds and intermediates of formulae I and IV: The compounds are useful as LRRK2 inhibitors in the treatment of LRRK2 mediated diseases, and as intermediates for their manufacture.
PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
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, (2012/05/31)
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the com
