| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GNE-8505 targets dual leucine zipper kinase (DLK), also known as MAP3K12. DLK is a serine/threonine kinase that belongs to the mixed-lineage kinase (MLK) family and is predominantly expressed in the nervous system. DLK acts as a key regulator of the c-Jun N-terminal kinase (JNK) signaling pathway, which is activated in response to various cellular stresses including axonal injury, oxidative stress, and neuroinflammation. Activation of DLK leads to phosphorylation of downstream MAP kinases, ultimately resulting in JNK activation and transcriptional changes that can promote either neuronal survival or degeneration depending on the context. Inhibition of DLK by GNE-8505 reduces JNK phosphorylation.
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| ln Vitro |
GNE-8505 is a potent inhibitor of DLK enzymatic activity. The compound demonstrates efficacy in cellular models of DLK-dependent signaling, reducing the phosphorylation of JNK, a downstream target of DLK. In vitro assays have confirmed that GNE-8505 effectively inhibits DLK kinase activity. The compound's oral bioavailability makes it suitable for in vivo studies. GNE-8505 is used to investigate the role of DLK in neuronal stress responses, axonal degeneration, and neuroprotection. The compound's ability to inhibit DLK with high potency allows researchers to dissect the specific contributions of DLK to JNK signaling and neurodegeneration.
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| ln Vivo |
GNE-8505 has demonstrated in vivo efficacy in a mouse model of optic nerve crush. Administration of GNE-8505 at doses of 3, 7, or 18 mg/kg decreased the levels of phosphorylated JNK in retinal lysates. This finding confirms that GNE-8505 engages its target DLK and inhibits downstream JNK signaling in vivo. The optic nerve crush model is a well-established model of axonal injury and neurodegeneration, and the ability of GNE-8505 to reduce JNK phosphorylation in this model supports its potential utility in neuroprotective strategies. The compound's oral availability further enhances its utility for in vivo studies. Detailed efficacy data, including effects on neuronal survival and functional outcomes, are available in the primary literature.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for GNE-8505 measures the inhibition of DLK kinase activity. Recombinant human DLK enzyme is incubated with varying concentrations of GNE-8505 (typically ranging from nanomolar to micromolar) in the presence of ATP and a peptide substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of substrate phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or radiometric measurement. IC50 values are determined by fitting dose-response curves to the inhibition data. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations, with DMSO concentration kept constant across all wells. Appropriate positive controls and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for GNE-8505 is performed using neuronal cell lines or primary neurons that express DLK and respond to DLK-mediated signaling. Cells are cultured in appropriate medium and treated with varying concentrations of GNE-8505 or vehicle control (DMSO). Cellular stress is induced by appropriate stimuli (e.g., trophic factor withdrawal, oxidative stress, or mechanical injury) to activate the DLK-JNK pathway. The phosphorylation status of JNK and other downstream signaling molecules is assessed by Western blotting or immunofluorescence. Cell viability and neurite integrity are evaluated to assess the neuroprotective effects of DLK inhibition. Dose-response relationships are established by analyzing the inhibition of JNK phosphorylation across different compound concentrations.
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| Animal Protocol |
In vivo animal experiments with GNE-8505 are typically conducted using the mouse optic nerve crush model. In this model, the optic nerve is subjected to a controlled crush injury to induce axonal degeneration and retinal ganglion cell death. GNE-8505 is administered orally at doses of 3, 7, or 18 mg/kg. Retinal lysates are prepared at specified time points after injury, and the levels of phosphorylated JNK are measured by Western blotting or ELISA to assess target engagement. Additional endpoints may include retinal ganglion cell survival (quantified by retrograde labeling or immunohistochemistry), axonal integrity, and functional outcomes such as visual evoked potentials. The compound is typically dosed daily or on a scheduled basis throughout the study period.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for GNE-8505 are not extensively documented in publicly available sources. However, GNE-8505 is described as an orally available inhibitor, indicating that it has adequate oral bioavailability for in vivo studies. The compound has a molecular weight of 419.44 and a chemical formula of C21H24F3N5O. It is soluble in acetonitrile (0.1-1 mg/mL). For in vivo administration, the compound is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored at -20°C for long-term stability. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for GNE-8505 are not extensively documented in publicly available sources. As a research-grade compound, GNE-8505 is intended for laboratory research purposes only and is not approved for human or veterinary use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. In animal studies, GNE-8505 has been administered at doses of 3, 7, and 18 mg/kg without reports of overt toxicity. However, comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
GNE-8505 is a research compound developed for studying the role of DLK in neurodegeneration and neuroprotection. DLK is a key regulator of the JNK signaling pathway, which is activated in response to axonal injury and other cellular stresses. GNE-8505 has demonstrated efficacy in reducing JNK phosphorylation in a mouse model of optic nerve crush, validating DLK as a therapeutic target for neuroprotection. The compound's oral availability enhances its utility for in vivo studies. GNE-8505 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical neuroscience research. The compound is available from various chemical suppliers for research purposes. Its utility lies in its ability to selectively inhibit DLK and probe its role in neuronal stress signaling.
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| Exact Mass |
419.193
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| CAS # |
1620573-48-9
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| PubChem CID |
90292687
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| Appearance |
White to off-white solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
645
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CC1CN2C(=CC(=N2)C3=CC(=C(N=C3)N)C(F)(F)F)C4[C@H]5[C@@H]4CN(C5)C6COC6
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| InChi Key |
IRPVABHDSJVBNZ-RTHVDDQRSA-N
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| InChi Code |
InChI=1S/C21H24F3N5O/c22-21(23,24)16-3-12(5-26-20(16)25)17-4-18(29(27-17)6-11-1-2-11)19-14-7-28(8-15(14)19)13-9-30-10-13/h3-5,11,13-15,19H,1-2,6-10H2,(H2,25,26)/t14-,15+,19?
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| Chemical Name |
5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine
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| Synonyms |
GNE-8505; GNE 8505; GNE8505
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~238.41 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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