5.06306

IKKε/TBK1 Inhibitor II, MRT67307

• 別名: IKKε/TBK1 Inhibitor II, MRT67307, N-(3-(5-Cyclopropyl-2-(3-(morpholinomethyl)phenylamino)pyrimidin-4-ylamino)propyl)cyclobutanecarboxamide, TANK Binding Kinase 1/IKK_inducible Inhibitor II, TANK Binding Kinase 1/IKK_inducible Inhibitor II, N-(3-(5-Cyclopropyl-2-(3-(morpholinomethyl)phenylamino)pyrimidin-4-ylamino)propyl)cyclobutanecarboxamide
• 実験式（ヒル表記法）: C₂₆H₃₆N₆O₂
• CAS番号: 1190378-57-4
• 分子量: 464.60
• MDL番号: MFCD19443643
• UNSPSCコード: 51111800
• NACRES: NA.77

特性

• アッセイ: ≥95% (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: amber
• 溶解性: DMSO: 100 mg/mL
• 保管温度: 2-8°C
• SMILES記法: N5(CCOCC5)Cc1cc(ccc1)Nc2nc(c(cn2)C4CC4)NCCCNC(=O)C3CCC3
• InChI: 1S/C26H36N6O2/c33-25(21-5-2-6-21)28-11-3-10-27-24-23(20-8-9-20)17-29-26(31-24)30-22-7-1-4-19(16-22)18-32-12-14-34-15-13-32/h1,4,7,16-17,20-21H,2-3,5-6,8-15,18H2,(H,28,33)(H2,27,29,30,31)
• InChI Key: UKBGBACORPRCGG-UHFFFAOYSA-N

詳細

詳細

A cell-permeable BX795 analog (>Cat. No. 204001) that acts as a potent, ATP-competitive, and reversible dual kinase inhibitor of TBK1/IKKε (IC₅₀ = 19 and 160 nM, respectively) with excellent selectivity over IKKα and IKKβ (IC₅₀ >10 µM). Interacts with the TBK1 kinase dimer interface and stabilizes the inactive DFG-out conformation. Also blocks the activity of MARK (microtubule- associated protein (MAP)-microtubule affinity regulating kinase) 1, 2, 3, and 4 (IC₅₀ = 27, 52, 36, and 41 nM, respectively), SIK2 (IC₅₀ = 67 nM) and Aurora B, JAK2, and MLK1,3 (> than 90% inhibition at 1 µM) in a 108-kinase panel. Increases TNF-α-stimulated NF-κB-dependent gene transcription in wild-type macrophages and enhances CREB-dependent gene transcription by promoting dephosphorylation of CREB-regulated transcription coactivator (CRTC3). Shown to aid TLR-stimulated production of anti-Inflammatory cytokines in macrophages while suppressing the secretion of pro-inflammatory cytokines. In response to pro-inflammatory stimuli, pre-treatment of BX795 robustly suppresses the activation of JNK and p38α, whereas MRT67307 does not exhibit such off-target effects.

A cell-permeable BX795 analog (>Cat. No. 204001) that acts as a potent, ATP-competitive, and reversible dual kinase inhibitor of TBK1/IKKε (IC₅₀ = 19 and 160 nM, respectively) with excellent selectivity over IKKα and IKKβ (IC₅₀ >10 µM). Interacts with the TBK1 kinase dimer interface and stabilizes the inactive DFG-out conformation. Also blocks the activity of MARK (microtubule- associated protein (MAP)-microtubule affinity regulating kinase) 1, 2, 3, and 4 (IC₅₀ = 27, 52, 36, and 41 nM, respectively), SIK2 (IC₅₀ = 67 nM) and Aurora B, JAK2, and MLK1,3 (> than 90% inhibition at 1 µM) in a 108-kinase panel. Increases TNF-α-stimulated NF-κB-dependent gene transcription in wild-type macrophages and enhances CREB-dependent gene transcription by promoting dephosphorylation of CREB-regulated transcription coactivator (CRTC3). Shown to aid TLR-stimulated production of anti-Inflammatory cytokines in macrophages while suppressing the secretion of pro-inflammatory cytokines. In response to pro-inflammatory stimuli, pre-treatment of BX795 robustly suppresses the activation of JNK and p38α, whereas MRT67307 does not exhibit such off-target effects.

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 and salt.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
TBK1 kinase dimer interface

Reversible: yes

Secondary Target
IKKe, MARK, SIK

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

その他情報

Bruni, D., et al. 2013. J. Immunol.190, 2844.
Tu, D., et al. Cell Reports3, 747.
Larabi, A., et al. Cell Reports3, 734.
Clark, K., et al. 2012. Proc. Natl. Acad. Sci. USA109, 16986.
Clark, K., et al. 2011. Proc. Natl. Acad. Sci. USA108, 17093.
Clark, K., et al. 2011. Biochem. J.434, 93.

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