5.33168

DLK Inhibitor, GNE-3511

• 別名: 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
• 実験式（ヒル表記法）: C₂₃H₂₆F₂N₆O
• CAS番号: 1496581-76-0
• 分子量: 440.49
• MDL番号: MFCD28502215
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• アッセイ: ≥98% (HPLC)
• 品質水準: 100
• フォーム: solid
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: yellow
• 溶解性: DMSO: 20 mg/mL
• 保管温度: 2-8°C
• SMILES記法: FC1(CN(CC1)c2nc(cc(c2)C4CCN(CC4)C5COC5)Nc3nccc(c3)C#N)F
• InChI: 1S/C23H26F2N6O/c24-23(25)4-8-31(15-23)22-11-18(17-2-6-30(7-3-17)19-13-32-14-19)10-21(29-22)28-20-9-16(12-26)1-5-27-20/h1,5,9-11,17,19H,2-4,6-8,13-15H2,(H,27,28,29)

詳細

詳細

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.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
DLK

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

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

その他情報

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

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable