5.33168

DLK Inhibitor, GNE-3511

• 别名: DLK Inhibitor, GNE-3511, MAP3K12 Inhibitor, GNE-3511, Dual Leucine Zipper Kinase, GNE-3511, GNE3511, GNE 3511, 2-((6-(3,3-Difluoropyrrolidin-1-yl)-4-(1-(oxetan-3-yl)piperidin-4-yl)pyridin-2-yl)amino)isonicotinonitrile
• 经验公式（希尔记法）: C₂₃H₂₆F₂N₆O
• CAS号: 1496581-76-0
• 分子量: 440.49
• 分類程式碼代碼: 12352200
• NACRES: NA.77

属性

• 化驗: ≥98% (HPLC)
• 品質等級: 100
• 形狀: solid
• 製造商／商標名: Calbiochem^®
• 儲存條件: OK to freeze; protect from light
• 顏色: yellow
• 溶解度: DMSO: 20 mg/mL
• 儲存溫度: 2-8°C

说明

一般說明

A cell-permeable, orally bioavailable, blood-brain barrier permeant 2,6-diaminopyridine based compound that acts as a highly potent and selective inhibitor of dual leucine zipper kinase inhibitor (DLK; K_i = 500 pM). Exhibits an ideal balance of metabolic stability, potency, and efflux properties. Displays high selectivity over JNK (IC₅₀ = 129, 514, and 364 nM for JNK1, 2, and 3, respectively) and MLK (IC₅₀ = 67.8, 767, and 602 nM for MLK1, 2, and 3, respectively). Does not affect the activities of MKK4 and MKK7 (IC₅₀ >5 µM). Protects neurons in an in vitro axon degeneration assay (IC₅₀ = 107 nM). Also shown to reduce levels of phosphorylated c-Jun in retina and offer protection in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) model of Parkinson′s disease. Exhibits desirable pharmacokinetic properties (t1/2 = 0.6 h; CLp = 56 ml/min/kg in mice; 1 mg/kg, i.v., or 5 mg/kg; p.o.).

A cell-permeable, orally bioavailable, blood-brain barrier permeant 2,6-diaminopyridine based compound that acts as a highly potent and selective inhibitor of dual leucine zipper kinase inhibitor (DLK; K_i = 500 pM). Exhibits an ideal balance of metabolic stability, potency, and efflux properties. Displays high selectivity over JNK (IC₅₀ = 129, 514, and 364 nM for JNK1, 2, and 3, respectively) and MLK (IC₅₀ = 67.8, 767, and 602 nM for MLK1, 2, and 3, respectively). Does not affect the activities of MKK4 and MKK7 (IC₅₀ >5 µM). Protects neurons in an in vitro axon degeneration assay (IC₅₀ = 107 nM). Also shown to reduce levels of phosphorylated c-Jun in retina and offer protection in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) model of Parkinson′s disease. Exhibits desirable pharmacokinetic properties (t1/2 = 0.6 h; CLp = 56 ml/min/kg in mice; 1 mg/kg, i.v., or 5 mg/kg; p.o.).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

生化／生理作用

Cell permeable: yes

Primary Target
DLK

Reversible: yes

包裝

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重構

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

其他說明

Patel, S., et al. 2014. J. Med. Chem. 57, in press.

法律資訊

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全信息

• 儲存類別代碼: 11 - Combustible Solids
• 水污染物質分類（WGK）: WGK 3
• 閃點（°F）: Not applicable
• 閃點（°C）: Not applicable