Identification of new NIK inhibitors by discriminatory analysis‐based molecular docking and biological evaluation

Cheng, Gang; Mei, Xiao‐Bing; Yan, Youyou; Chen, Jing; Zhang, Bo; Li, Jia; Dong, Xiaowu; Lin, Nengming; Zhou, Yubo

doi:10.1002/ardp.201800374

Cited by 12 publications

(7 citation statements)

References 30 publications

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“…As a continuation of our virtual screening work which identified new inhibitors targeting NIK, CHK1, Akt, etc. (18)(19)(20)(21)(22)(23)(24). In this study, we performed a traditional VS procedure to identify potential inhibitors of IRAK1.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Artificial Intelligence in Participating Structure-Based Virtual Screening for Identifying Novel Interleukin-1 Receptor Associated Kinase-1 Inhibitors

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Evaluation of Artificial Intelligence in Participating Structure-Based Virtual Screening for Identifying Novel Interleukin-1 Receptor Associated Kinase-1 Inhibitors

et al. 2020

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“…One year later, a new NIK-targeting compound was identified by Cheng et al. with a relatively high IC50 value ( 76 ). It would be interesting to test this inhibitor in a B cell malignancy model for more accurate comparison.…”

Section: Overview Of In Vitro Nik Inhibitorsmentioning

confidence: 99%

The Therapeutic Potential of Targeting NIK in B Cell Malignancies

Haselager

Eldering

2022

Front. Immunol.

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NF-κB-inducing kinase (NIK) is a key player in non-canonical NF-κB signaling, involved in several fundamental cellular processes, and is crucial for B cell function and development. In response to certain signals and ligands, such as CD40, BAFF and lymphotoxin-β activation, NIK protein stabilization and subsequent NF-κB activation is achieved. Overexpression or overactivation of NIK is associated with several malignancies, including activating mutations in multiple myeloma (MM) and gain-of-function in MALT lymphoma as a result of post-translational modifications. Consequently, drug discovery studies are devoted to pharmacologic modulation of NIK and development of specific novel small molecule inhibitors. However, disease-specific in vitro and in vivo studies investigating NIK inhibition are as of yet lacking, and clinical trials with NIK inhibitors remain to be initiated. In order to bridge the gap between bench and bedside, this review first briefly summarizes our current knowledge on NIK activation, functional activity and stability. Secondly, we compare current inhibitors targeting NIK based on efficacy and specificity, and provide a future perspective on the therapeutic potential of NIK inhibition in B cell malignancies.

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“…Computer-aided drug design has shown to be an effective approach to identify novel GSK-3 inhibitors [29]. Recently, various methods have been explored to improve the discriminatory ability of molecular docking [30][31][32]. Herein, we reported the identification of 3 novel inhibitors of GSK-3β from Specs database through a discriminatory analysis-based molecular docking and in vitro enzymatic experiment.…”

Section: Identification Of Novel Gsk-3β Inhibitors Through Docking Based Virtual Screening and Biological Evaluationmentioning

confidence: 99%

Identification of Novel GSK-3β Inhibitors through Docking Based Virtual Screening and Biological Evaluation

Xu¹,

Sy²,

Yx³

et al. 2021

austinjcancerclinres

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GSK-3β is a key regulator in insulin, Wnt and NF-κB signaling pathways. Dysregulation of GSK-3β is often related to tumors and diabetes. Inhibiting it might provide cure for diabetes, tumors, neurodegeneration and brain ischemia. Although there are a number of reported GSK-3β inhibitors, the scaffold is limited. Herein we report a discriminatory analysis-based molecular docking on the Specs database, and identiﬁed 3 novel GSK-3β inhibitors with moderate IC50 (ranging from 17.42 μM to 6.74 μM) in the following in vitro biological test. Further dynamic simulations and docking pose analysis were performed to give a better understanding on the binding conformation of 3 hit compounds AK- 777/09836064, AK-968/37185006 and AN-698/41607072, which would provide basis for further optimization.

show abstract

Identification of new NIK inhibitors by discriminatory analysis‐based molecular docking and biological evaluation

Cited by 12 publications

References 30 publications

Evaluation of Artificial Intelligence in Participating Structure-Based Virtual Screening for Identifying Novel Interleukin-1 Receptor Associated Kinase-1 Inhibitors

Evaluation of Artificial Intelligence in Participating Structure-Based Virtual Screening for Identifying Novel Interleukin-1 Receptor Associated Kinase-1 Inhibitors

The Therapeutic Potential of Targeting NIK in B Cell Malignancies

Identification of Novel GSK-3β Inhibitors through Docking Based Virtual Screening and Biological Evaluation

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