scholarly journals Cell-Permeable Bicyclic Peptidyl Inhibitors against NEMO-IκB Kinase Interaction Directly from a Combinatorial Library

2018 ◽  
Vol 140 (38) ◽  
pp. 12102-12110 ◽  
Author(s):  
Curran A. Rhodes ◽  
Patrick G. Dougherty ◽  
Jahan K. Cooper ◽  
Ziqing Qian ◽  
Steffen Lindert ◽  
...  
Keyword(s):  
Combinatorial Library ◽  
Iκb Kinase ◽  
Peptidyl Inhibitors

scholarly journals Cell-permeable bicyclic peptidyl inhibitors against T-cell protein tyrosine phosphatase from a combinatorial library

2017 ◽  
Vol 15 (45) ◽  
pp. 9595-9598 ◽  
Author(s):  
Hui Liao ◽  
Dehua Pei
Keyword(s):  
T Cell ◽  
Protein Tyrosine Phosphatase ◽  
Combinatorial Library ◽  
Tyrosine Phosphatase ◽  
Biologically Active ◽  
Cell Protein ◽  
Protein Tyrosine ◽  
Peptidyl Inhibitors

Cell-permeable, biologically active bicyclic peptidyl inhibitors against T-cell protein-tyrosine phosphatase were directly isolated from a combinatorial library.

Author response for "Icaritin inhibits PD‐L1 Expression by Targeting Protein IκB Kinase α"

2020 ◽  
Author(s):  
Dongliang Mo ◽  
Hai Zhu ◽  
Jun Wang ◽  
Haibang Hao ◽  
Yuming Guo ◽  
...  
Keyword(s):  
Author Response ◽  
Iκb Kinase

Insilico studies, synthesis and antitubercular activity of some novel quinoline – azitidinone derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Trupti. S. Chitre ◽  
Kalyani. D. Asgaonkar ◽  
Amrut B. Vikhe ◽  
Shital M Patil ◽  
Dinesh. R. Garud ◽  
...  
Keyword(s):  
Combinatorial Library ◽  
3D Qsar ◽  
Antitubercular Activity ◽  
Structural Features ◽  
Docking Studies ◽  
Quinoline Derivatives ◽  
Qsar Models ◽  
Molecular Modeling Studies ◽  
Lead Generation ◽  
Mcf 7

Background: Diarylquinolines like Bedaquiline have shown promising antitubercular activity by their action of Mycobacterial ATPase. Objective: The structural features necessary for good antitubercular activity for a series of quinoline derivatives were explored through computational chemistry tools like QSAR and combinatorial library generation. In the current study, 3-Chloro-4-(2-mercaptoquinoline-3-yl)-1-substitutedphenylazitidin-2-one derivatives have been designed and synthesized based on molecular modeling studies as anti-tubercular agents. Method: 2D and 3DQSAR analysis was used to designed compounds having quinoline scaffold. The synthesized compounds were evaluated against active and dormant strains of Mycobacterium tuberculosis (MTB) H37 Ra and Mycobacterium bovis BCG. The compounds were also tested for cytotoxicity against MCF-7, A549 and Panc-1 cell lines using MTT assay. Binding affinity of designed compounds was gauged by molecular docking studies. Results: Statistically significant QSAR models generated by SA-MLR method for 2D QSAR exhibited r2 = 0.852, q2 = 0.811and whereas 3D QSAR with SA-kNN showed q2 = 0.77. The synthesized compounds exhibited MIC in the range of 1.38-14.59(µg/ml) .These compounds showed some crucial interaction with MTB Atpase. Conclusion: The present study has shown some promising results which can be further explored for lead generation.

scholarly journals Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy

2021 ◽  
Vol 7 (4) ◽  
pp. eabc5539
Author(s):  
Xing Li ◽  
Qian Xia ◽  
Meng Mao ◽  
Huijuan Zhou ◽  
Lu Zheng ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Underlying Mechanism ◽  
Nuclear Factor Κb ◽  
Annexin A1 ◽  
Selective Autophagy ◽  
Microglial Polarization ◽  
Proinflammatory Mediators ◽  
Therapeutic Benefits ◽  
Iκb Kinase ◽  
Ikk Complex

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.

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