Basic information Description References Safety Supplier Related

GNE-3511

Basic information Description References Safety Supplier Related

GNE-3511 Basic information

Product Name:
GNE-3511
Synonyms:
  • 2-[[6-(3,3-difluoropyrrolidin-1-yl)-4-[1-(oxetan-3-yl)piperidin-4-yl]pyridin-2-yl]amino]pyridine-4-carbonitrile
  • 2-{[6-(3,3-DIFLUOROPYRROLIDIN-1-YL)-4-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRIDIN-2-YL]AMINO}PYRIDINE-4-CARBONITRILE
  • CS-2506
  • GNE3511;GNE 3511
  • GNE-3511
  • 2-((6-(3,3-DIFLUOROPYRROLIDIN-1-YL)-4-(1-(OXETAN-3-YL)PIPERIDIN-4-YL)PYRIDIN-2-YL)AMINO)ISONICOTINONITRILE
  • 4-Pyridinecarbonitrile, 2-[[6-(3,3-difluoro-1-pyrrolidinyl)-4-[1-(3-oxetanyl)-4-piperidinyl]-2-pyridinyl]amino]-
  • GNE35Chemicalbook11
CAS:
1496581-76-0
MF:
C23H26F2N6O
MW:
440.49
Product Categories:
  • API
Mol File:
1496581-76-0.mol
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GNE-3511 Chemical Properties

Boiling point:
579.0±50.0 °C(Predicted)
Density 
1.37±0.1 g/cm3(Predicted)
storage temp. 
Store at -20°C
solubility 
DMSO:25.63(Max Conc. mg/mL);58.18(Max Conc. mM)
Methanol:1.0(Max Conc. mg/mL);2.27(Max Conc. mM)
form 
A crystalline solid
pka
7.23±0.40(Predicted)
color 
Light yellow to yellow
InChIKey
RHFIAUKMKYHHFA-UHFFFAOYSA-N
SMILES
C1(NC2=NC(N3CCC(F)(F)C3)=CC(C3CCN(C4COC4)CC3)=C2)=NC=CC(C#N)=C1
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Safety Information

HS Code 
2934999090
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GNE-3511 Usage And Synthesis

Description

GNE-3511 is a selective and highly potent inhibitor of dual leucine zipper kinase (DLK). It also inhibits phosphorylated JNKand is highly selective for DLK over other MAP kinases. In an MPTP mouse model of Parkinson’s disease, a high dose of GNE-3511 completely suppresses phosphorylated c-Jun (p-c-Jun) expression, while a low dose moderately reduces its expression. Study has also shown that GNE03511 displayed concentration-dependent protection of neurons from degeneration in vitro and demonstrated dose-dependent activity in two different animal models of disease. These results suggest that GNE-3511 may have therapeutic potential in multiple indications.

References

Patel, S, et al. "Discovery of Dual Leucine Zipper Kinase (DLK, MAP3K12) Inhibitors with Activity in Neurodegeneration Models. " Journal of Medicinal Chemistry 58.1(2015):401-18.
https://www.caymanchem.com/product/19174

Uses

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.

Biological Activity

Cell permeable: yes', 'Primary Target
DLK', 'Reversible: yes

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/kgVdss (L/kgt1/2 (h)F (%)Bu/PuCSF/Pu
mouse562.50.6450.24 at 6 h
rat303.71.8630.70.4
dog416.54320.4
cynomolgous163.12.4190.6
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.

GNE-3511Supplier

Chengdu Celes Technology Co., Ltd Gold
Tel
19982073091
Email
2538834896@qq.com
Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
ShangHai Caerulum Pharma Discovery Co., Ltd.
Tel
18149758185
Email
sales-cpd@caerulumpharma.com
Shanghai Lollane Biological Technology Co.,Ltd.
Tel
021-52996696，15000506266 15000506266
Shanghaizehan biopharma technology co., Ltd.
Tel
021-61350663 13052117465
Email
sales@zehanbiopharma.com
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