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[CAS NO. 1496581-76-0] GNE-3511
| Ships within | Stock | Price | Qty | Total |
Please click "REQUEST A QUOTE" button if there is no stock, or you need other sizes or custom synthesis.
| Catalog: | HY-12947 |
| Brand: | MCE |
| CAS: | 1496581-76-0 |
Overview
| MDL | MFCD28502215 |
|---|---|
| Molecular Weight | 440.49 |
| Molecular Formula | C23H26F2N6O |
| SMILES | N#CC1=CC=NC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=C1 |
6 Publications Citing Use of MCE
- [1]Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9899-E9908.
- [2]Cell Rep. 2019 Sep 3;28(10):2581-2593.e5.
- [3]Neurobiol Dis. 2021 Dec 16;105586.
- [4]J Innate Immun. 2021 Jun 25;1-10.
- [5]Patent. US20230014181.
- [6]Washington State University. Division of Biology and Biomedical Sciences Neurosciences. 2021 Oct.
Summary
GNE-3511 is an orally active bioavailable and brain-penetrant dual leucine zipper kinase (DLK) inhibitor with a K i 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]
In Vitro
GNE-3511 has inhibitory activity for p-JNK and DRG with IC
50
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 IC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 | CL p (mL/min/kg | Vd ss (L/kg | t 1/2 (h) | F (%) | B u /P u | CSF/P u |
| 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 |
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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 31.25 mg/mL ( 70.94 mM ; Need ultrasonic)
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 |
| 10 mM | 0.2270 mL | 1.1351 mL | 2.2702 mL |
-
1.
References
- [1] Patel S et al. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18.
- [2] Chen Jiang, et al. Neuronal Dual Leucine Zipper Kinase Mediates Inflammatory and Nociceptive Responses in Cyclophosphamide-Induced Cystitis. J Innate Immun
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