GNE-3511
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MedKoo CAT#: 522419

CAS#: 1496581-76-0

Description: 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.


Chemical Structure

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GNE-3511
CAS# 1496581-76-0

Theoretical Analysis

MedKoo Cat#: 522419
Name: GNE-3511
CAS#: 1496581-76-0
Chemical Formula: C23H26F2N6O
Exact Mass: 440.21
Molecular Weight: 440.500
Elemental Analysis: C, 62.71; H, 5.95; F, 8.63; N, 19.08; O, 3.63

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 850 Ready to ship
500mg USD 1850 Ready to ship
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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

Appearance: Solid powder

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

More Info:

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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.6 58.18
Methanol 1.0 2.27

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.

Recalculate based on batch purity %
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.

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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.