1496581-76-0 Usage
Description
GNE-3511 is a selective and highly potent inhibitor of dual leucine zipper kinase (DLK). It also inhibits phosphorylated JNKand is highly selective for DLK over other MAP kinases. In an MPTP mouse model of Parkinson’s disease, a high dose of GNE-3511 completely suppresses phosphorylated c-Jun (p-c-Jun) expression, while a low dose moderately reduces its expression. Study has also shown that GNE03511 displayed concentration-dependent protection of neurons from degeneration in vitro and demonstrated dose-dependent activity in two different animal models of disease. These results suggest that GNE-3511 may have therapeutic potential in multiple indications.
References
Patel, S, et al. "Discovery of Dual Leucine Zipper Kinase (DLK, MAP3K12) Inhibitors with Activity in Neurodegeneration Models. " Journal of Medicinal Chemistry 58.1(2015):401-18.
https://www.caymanchem.com/product/19174
Uses
GNE-3511 is a potent and selective dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. GNE-3511 displays concentration-dependent protection of neurons from degeneration in vitro and demonstrated dose-dependent activity in two different animal models of disease. GNE-3511 displays protection of primary neurons in an in vitro axon degeneration assay as well as activity in the mouse models of glaucoma/optic neuropathy (optic nerve crush) and Parkinson’s disease (MPTP) after oral dosing.
Check Digit Verification of cas no
The CAS Registry Mumber 1496581-76-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,9,6,5,8 and 1 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1496581-76:
(9*1)+(8*4)+(7*9)+(6*6)+(5*5)+(4*8)+(3*1)+(2*7)+(1*6)=220
220 % 10 = 0
So 1496581-76-0 is a valid CAS Registry Number.
1496581-76-0Relevant articles and documents
Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models
Patel, Snahel,Cohen, Frederick,Dean, Brian J.,De La Torre, Kelly,Deshmukh, Gauri,Estrada, Anthony A.,Ghosh, Arundhati Sengupta,Gibbons, Paul,Gustafson, Amy,Huestis, Malcolm P.,Le Pichon, Claire E.,Lin, Han,Liu, Wendy,Liu, Xingrong,Liu, Yichin,Ly, Cuong Q.,Lyssikatos, Joseph P.,Ma, Changyou,Scearce-Levie, Kimberly,Shin, Young G.,Solanoy, Hilda,Stark, Kimberly L.,Wang, Jian,Wang, Bei,Zhao, Xianrui,Lewcock, Joseph W.,Siu, Michael
, p. 401 - 418 (2015/01/30)
Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding mode and specific design parameters to optimize for CNS druglike molecules, we came to focus on the di(pyridin-2-yl)amines because of their combination of desirable potency and good brain penetration following oral dosing. Our lead inhibitor GNE-3511 (26) displayed concentration-dependent protection of neurons from degeneration in vitro and demonstrated dose-dependent activity in two different animal models of disease. These results suggest that specific pharmacological inhibition of DLK may have therapeutic potential in multiple indications.
