Pyrazolo(4,3-c)isoquinolines as potential inhibitors of NF-kappaB activation.

Mortier J; Frederick R; Ganeff C; Remouchamps C; Talaga P; Pochet L; Wouters J; Piette J; Dejardin E; Masereel B

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Pyrazolo(4,3-c)isoquinolines as potential inhibitors of NF-kappaB activation.

机译：吡唑啉（4,3-c）异喹啉类化合物是NF-κB活化的潜在抑制剂。

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In this work, we aimed to build a 3D-model of NIK and to study the binding of pyrazolo[4,3-c]isoquinolines with a view to highlight the structural elements responsible for their inhibitory potency. However, in the course of this work, we unexpectedly found that the pyrazolo[4,3-c]isoquinolines initially reported as NIK inhibitors were neither inhibitors of this enzyme nor of the alternative NF-kappaB pathway, but were in fact inhibitors of another kinase, the TGF-beta activated kinase 1 (TAK1) which is involved in the classical NF-kappaB pathway.

机译：在这项工作中，我们旨在建立NIK的3D模型并研究吡唑并[4,3-c]异喹啉的结合，以期突出引起其抑制效力的结构元件。然而，在这项工作的过程中，我们意外地发现最初报道为NIK抑制剂的吡唑并[4,3-c]异喹啉既不是该酶的抑制剂，也不是替代的NF-κB途径的抑制剂，但实际上是另一种抑制剂激酶，即TGF-β活化激酶1（TAK1），参与经典的NF-κB途径。

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《Biochemical Pharmacology》 |2010年第10期|共11页
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Mortier J; Frederick R; Ganeff C; Remouchamps C; Talaga P; Pochet L; Wouters J; Piette J; Dejardin E; Masereel B;
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1. Pyrazolo(4,3-c)isoquinolines as potential inhibitors of NF-kappaB activation. [J] . Mortier J, Frederick R, Ganeff C, Biochemical Pharmacology . 2010,第10期

机译：吡唑啉（4,3-c）异喹啉类化合物是NF-κB活化的潜在抑制剂。
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3. Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents [J] . Francis Stuart, Croft Daniel, Schtittelkopf Alexander W., Bioorganic and Medicinal Chemistry Letters . 2019,第8期

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4. QSAR Study of Some Pyrazolo［3,4-d］pyrimidine Derivatives as the c-Src Inhibitors [C] . Bindesh Kumar Shukla, Umesh Yadava International Conference on Condensed Matter and Applied Physics . 2016

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5. Beta2 Integrins Inhibit TLR Responses by Reducing NF-kappaB Pathway Activation. [D] . Yee, Nathan Ken. 2012

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6. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. [O] . H Y Song, M Rothe, D V Goeddel 1996

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7. Synthesis of pyridyl substituted pyrazolo[4,3-c]pyridines as potential inhibitors of protein kinases [O] . Wolfgang Holzer A 2014

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8. Assessment of Nanobiotechnology-Targeted siRNA Designed to Inhibit NF-KappaB Classical and Alternative Signaling in Breast Tumor Macrophages. [R] . Yull, F. 2014

机译：纳米生物技术靶向siRNa的评估旨在抑制乳腺肿瘤巨噬细胞中NF-κB经典和替代信号。

Pyrazolo(4,3-c)isoquinolines as potential inhibitors of NF-kappaB activation.

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