Discovery of a potent peptidic cyclophilin A inhibitor Trp-Gly-Pro

Pang, Xiaodong; Zhang, Mingjun; Zhou, Lei; Xie, Fang; Liang, Hong; He, Wei; Jiang, Shibo; Liu, Yu; Zhang, Xinyi

doi:10.1016/j.ejmech.2011.02.023

Cited by 10 publications

(3 citation statements)

References 22 publications

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“…However, CypA was the protein that exhibited the most significant p value (0.000000019). CypA has been found to participate in the replication of several viruses. − …”

Section: Results and Discussionmentioning

confidence: 99%

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

et al. 2017

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Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in cells treated with both inhibitors using reporter BHK-21-rep-YFV17D-LucNeoIres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction.

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“…However, CypA was the protein that exhibited the most significant p value (0.000000019). CypA has been found to participate in the replication of several viruses. − …”

Section: Results and Discussionmentioning

confidence: 99%

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

et al. 2017

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“…SPR is a label-free and real-time detection method for monitoring biomolecular interactions [40] . In recent years, SPR has become a rapid developmental technology for studying the interaction between membrane protein receptors and ligands [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , which is shown in Table 2 . Because of the high-throughput screening characteristic, SPR has been widely used in the identification of drug targets and the optimization of lead compounds [44] , [45] , [46] , [47] , [48] .…”

Section: Surface Plasmon Resonance Techniquementioning

confidence: 99%

Overview of the detection methods for equilibrium dissociation constant KD of drug-receptor interaction

Yang

2018

Journal of Pharmaceutical Analysis

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Drug-receptor interaction plays an important role in a series of biological effects, such as cell proliferation, immune response, tumor metastasis, and drug delivery. Therefore, the research on drug-receptor interaction is growing rapidly. The equilibrium dissociation constant (KD) is the basic parameter to evaluate the binding property of the drug-receptor. Thus, a variety of analytical methods have been established to determine the KD values, including radioligand binding assay, surface plasmon resonance method, fluorescence energy resonance transfer method, affinity chromatography, and isothermal titration calorimetry. With the invention and innovation of new technology and analysis method, there is a deep exploration and comprehension about drug-receptor interaction. This review discusses the different methods of determining the KD values, and analyzes the applicability and the characteristic of each analytical method. Conclusively, the aim is to provide the guidance for researchers to utilize the most appropriate analytical tool to determine the KD values.

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“…Also, WGP inhibits cyclophilin A-mediated PPIase activity with IC 50 values of 33.11 nM and 10.25 nM, respectively. In addition, this peptide also inhibits HIV-1 infection and exhibits lower toxicity and better oral availability and solubility than CsA, making it a potential CsA replacement in clinical applications [ 164 ].…”

Section: Peptide Analoguesmentioning

confidence: 99%

Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers

Zhao,

et al. 2024

Molecules

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Cyclophilin A, a widely prevalent cellular protein, exhibits peptidyl-prolyl cis-trans isomerase activity. This protein is predominantly located in the cytosol; additionally, it can be secreted by the cells in response to inflammatory stimuli. Cyclophilin A has been identified to be a key player in many of the biological events and is therefore involved in several diseases, including vascular and inflammatory diseases, immune disorders, aging, and cancers. It represents an attractive target for therapeutic intervention with small molecule inhibitors such as cyclosporin A. Recently, a number of novel inhibitors of cyclophilin A have emerged. However, it remains elusive whether and how many cyclophilin A inhibitors function in the inflammatory diseases and cancers. In this review, we discuss current available data about cyclophilin A inhibitors, including cyclosporin A and its derivatives, quinoxaline derivatives, and peptide analogues, and outline the most recent advances in clinical trials of these agents. Inhibitors of cyclophilin A are poised to enhance our comprehension of the molecular mechanisms that underpin inflammatory diseases and cancers associated with cyclophilin A. This advancement will aid in the development of innovative pharmaceutical treatments in the future.

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Discovery of a potent peptidic cyclophilin A inhibitor Trp-Gly-Pro

Cited by 10 publications

References 22 publications

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

Overview of the detection methods for equilibrium dissociation constant KD of drug-receptor interaction

Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers

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