GNE-3511 | CAS#1496581-76-0 | DLK and MAP3K12 inhibitor

MedKoo Cat#: 522419 | Name: GNE-3511

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

GNE-3511

CAS#1496581-76-0

Theoretical Analysis

MedKoo Cat#: 522419

Name: GNE-3511

CAS#: 1496581-76-0

Chemical Formula: C23H26F2N6O

Exact Mass: 440.2136

Molecular Weight: 440.50

Elemental Analysis: C, 62.71; H, 5.95; F, 8.63; N, 19.08; O, 3.63

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,850.00	Ready to ship

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Related CAS #

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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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C7R09B18

View CoA: current batch, Lot#C9R12B26

View CoA: current batch, Lot#CRB70424

QC Data

View QC data: current batch, Lot#C7R09B18

View QC data: current batch, Lot#C9R12B26

View QC data: current batch, Lot#CRB70424

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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
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:

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. PubMed PMID: 25341110.