GNE-3511

SKU: orb1226184

Description

GNE-3511 is a potent, selective, orally bioavailable, brain-penetrant dual leucine zipper kinase (DLK, MAP3K12) inhibitor with Ki of 100-fold selectivity over MKK4/7, JNK1/2/3, MLK1/2/3; inhibits p-JNK with IC50 of 30 nM, displays concentration-dependent protection of neurons from degeneration in vitro (DRG IC50=107 nM) and demonstrates dose-dependent activity in multiple animal models of neurodegenerative disease.

Key Properties

• CAS Number: 1496581-76-0
• MW: 440.489
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₆F₂N₆O
• SMILES: N#CC1=CC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=NC=C1
• Target: MEK
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• In Vivo:
  GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced nociceptive behavior by inhibiting DLK in mice. GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced edema and hemorrhage in mouse bladder. GNE-3511 (iv. ; 1 mg/kg or po. ; 5 mg/kg) exhibits moderate In vivo plasmaclearances, moderate volumes of distribution, short half-lives, and brain penetration. Animal model: Cystitis mouse model. 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. 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.
• In Vitro:
  GNE-3511 has inhibitory activity for p-JNK and DRG with IC50 values of 30 nM and 107 nM, respectively. 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. GNE-3511 displays concentration-dependent protection of neurons from degeneration in vitro.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GNE3511 | GNE 3511

Quick Database Links

Gene Symbol

MEK