Synonym
GNE-3511; GNE 3511; GNE3511.
IUPAC/Chemical Name
2-((6-(3,3-difluoropyrrolidin-1-yl)-4-(1-(oxetan-3-yl)piperidin-4-yl)pyridin-2-yl)amino)isonicotinonitrile
InChi Key
RHFIAUKMKYHHFA-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H26F2N6O/c24-23(25)4-8-31(15-23)22-11-18(17-2-6-30(7-3-17)19-13-32-14-19)10-21(29-22)28-20-9-16(12-26)1-5-27-20/h1,5,9-11,17,19H,2-4,6-8,13-15H2,(H,27,28,29)
SMILES Code
N#CC1=CC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=NC=C1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
GNE-3511 is a dual leucine zipper kinase (DLK) inhibitor with a Ki of 0.5 nM.
In vitro activity:
Dual leucine zipper kinase (DLK, MAP3K12) was identified as an essential regulator of neuronal degeneration in multiple contexts. The DLK inhibitor GNE-3511 displayed concentration-dependent protection of neurons from degeneration in vitro. These results suggest that specific pharmacological inhibition of DLK may have therapeutic potential in multiple indications.
Reference: J Med Chem. 2015 Jan 8;58(1):401-18. https://pubs.acs.org/doi/10.1021/jm5013984
In vivo activity:
Using proposed hinge-binding interactions to infer a binding mode and specific design parameters to optimize for CNS druglike molecules, the di(pyridin-2-yl)amines were evaluated because of their combination of desirable potency and good brain penetration following oral dosing. GNE-3511 demonstrated dose-dependent activity in two different animal models of disease.
Reference: J Med Chem. 2015 Jan 8;58(1):401-18. https://pubs.acs.org/doi/10.1021/jm5013984
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
25.6 |
58.18 |
|
| Methanol |
1.0 |
2.27 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
440.50
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP, Le Pichon CE, Lin H, Liu W, Liu X, Liu Y, Ly CQ, Lyssikatos JP, Ma C, Scearce-Levie K, Shin YG, Solanoy H, Stark KL, Wang J, Wang B, Zhao X, Lewcock JW, Siu M. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. PMID: 25341110.
In vitro protocol:
1. Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP, Le Pichon CE, Lin H, Liu W, Liu X, Liu Y, Ly CQ, Lyssikatos JP, Ma C, Scearce-Levie K, Shin YG, Solanoy H, Stark KL, Wang J, Wang B, Zhao X, Lewcock JW, Siu M. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. PMID: 25341110.
In vivo protocol:
1. Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP, Le Pichon CE, Lin H, Liu W, Liu X, Liu Y, Ly CQ, Lyssikatos JP, Ma C, Scearce-Levie K, Shin YG, Solanoy H, Stark KL, Wang J, Wang B, Zhao X, Lewcock JW, Siu M. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. PMID: 25341110.
1: Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP, Le Pichon CE, Lin H, Liu W, Liu X, Liu Y, Ly CQ, Lyssikatos JP, Ma C, Scearce-Levie K, Shin YG, Solanoy H, Stark KL, Wang J, Wang B, Zhao X, Lewcock JW, Siu M. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. PubMed PMID: 25341110.
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