2. MAPK/ERK Pathway
  3. MAP3K
  4. GNE-3511

GNE-3511 is an orally active bioavailable and brain-penetrant dual leucine zipper kinase (DLK) inhibitor with a Ki of 0.5 nM. GNE-3511 can cross the blood-brain-barrier and can be used for the research of neurodegenerative diseases.

For research use only. We do not sell to patients.

GNE-3511 Chemical Structure

GNE-3511 Chemical Structure

CAS No. : 1496581-76-0

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 99 In-stock
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10 mM * 1 mL in DMSO USD 99 In-stock
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5 mg USD 58 In-stock
10 mg USD 90 In-stock
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Customer Review

Based on 7 publication(s) in Google Scholar

GNE-3511 Related Antibodies

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  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

GNE-3511 is an orally active bioavailable and brain-penetrant dual leucine zipper kinase (DLK) inhibitor with a Ki of 0.5 nM. GNE-3511 can cross the blood-brain-barrier and can be used for the research of neurodegenerative diseases[1].

IC50 & Target

Ki: 0.5 nM (DLK); IC50: 30 nM (p-JNK), 107 nM (DRG); ＞5000 nM (MKK4), ＞5000 nM (MKK7), 129 nM (JNK1),514 nM (JNK2), 364 nM (JNK3), 67.8 nM (MLK1), 767 nM (MLK2) and 602 nM (MLK3)[1]
Cellular Effect
Cell Line Type Value Description References
HEK293 IC50
30 nM
Compound: 26, GNE-3511
Inhibition of human DLK transfected in HEK293 cells assessed as JNK phosphorylation after 5.5 hrs by Hoechst-33342 staining-based assay
Inhibition of human DLK transfected in HEK293 cells assessed as JNK phosphorylation after 5.5 hrs by Hoechst-33342 staining-based assay
[PMID: 25341110]
In Vitro

GNE-3511 has inhibitory activity for p-JNK and DRG with IC50 values of 30 nM and 107 nM, respectively[1].
GNE-3511 has kinase selectivity for MKK4, MKK7, JNK1, JNK2, JNK3, MLK1, MLK2 and MLK3 with IC50 values of ＞5000 nM, ＞5000 nM, 129 nM, 514 nM, 364 nM, 67.8 nM, 767 nM and 602 nM, respectively[1].
GNE-3511 displays concentration-dependent protection of neurons from degeneration in vitro[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

GNE-3511 Related Antibodies
In Vivo

GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced nociceptive behavior by inhibiting DLK in mice[2].
GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced edema and hemorrhage in mouse bladder[2].
GNE-3511 (iv.; 1 mg/kg or po.; 5 mg/kg) exhibits moderate in vivo plasma clearances, moderate volumes of distribution, short half-lives, and brain penetration[2].
Pharmacokinetic Parameters of GNE-3511 (iv.; 1 mg/kg or po.; 5 mg/kg)[2].

species CLp (mL/min/kg Vdss (L/kg t1/2 (h) F (%) Bu/Pu CSF/Pu
mouse 56 2.5 0.6 45 0.24 at 6 h
rat 30 3.7 1.8 63 0.7 0.4
dog 41 6.5 4 32 0.4
cynomolgous 16 3.1 2.4 19 0.6

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Cystitis mouse model[1]
Dosage: 75 mg/kg
Administration: oral gavage;75 mg/kg; single
Result: Significantly reduced the number of nociceptive behavior as well as nociceptive score.
Had no impact on bladder weight, did not induce bladder edema or hemorrhage and significantly suppressed CYP-induced increase in bladder weight, bladder edema, and hemorrhage.
Animal Model: mouse, rat, cynomolgus and dog[2]
Dosage: 1 mg/k, 5 mg/kg
Administration: iv.; 1 mg/kg or po.; 5 mg/kg
Result: Exhibited moderate in vivo plasma clearances, moderate volumes of distribution, short half-lives and brain penetration.
Molecular Weight

440.49

Formula

C23H26F2N6O
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

N#CC1=CC=NC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=C1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 1 year
-20°C 6 months
Solvent & Solubility
In Vitro: 

DMSO : 31.25 mg/mL (70.94 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.2702 mL 11.3510 mL 22.7020 mL
5 mM 0.4540 mL 2.2702 mL 4.5404 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.08 mg/mL (4.72 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

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(per animal)

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(per animal)

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.07%

SDS (393 KB)

COA (248 KB) HNMR (271 KB) LCMS (266 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.2702 mL 11.3510 mL 22.7020 mL 56.7550 mL
5 mM 0.4540 mL 2.2702 mL 4.5404 mL 11.3510 mL
10 mM 0.2270 mL 1.1351 mL 2.2702 mL 5.6755 mL
15 mM 0.1513 mL 0.7567 mL 1.5135 mL 3.7837 mL
20 mM 0.1135 mL 0.5675 mL 1.1351 mL 2.8377 mL
25 mM 0.0908 mL 0.4540 mL 0.9081 mL 2.2702 mL
30 mM 0.0757 mL 0.3784 mL 0.7567 mL 1.8918 mL
40 mM 0.0568 mL 0.2838 mL 0.5675 mL 1.4189 mL
50 mM 0.0454 mL 0.2270 mL 0.4540 mL 1.1351 mL
60 mM 0.0378 mL 0.1892 mL 0.3784 mL 0.9459 mL
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GNE-3511 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

GNE-35111496581-76-0GNE3511GNE 3511MAP3KMAP kinase kinase kinase, MEKK, MAPKKKoralbrain-penetrantdual leucine zipper kinase (DLK)blood-brain-barrierneurodegenerative diseasesInhibitorinhibitorinhibit

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