Targeting Extracellular Cyclophilin A via an Albumin‐Binding Cyclosporine A Analogue

Liu, Siyu; Zhang, Qingzhou; Hu, Minqiang; Li, Fengxia; Fu, Jiamiao; Zhu, Zhendong; Li, Qinkai; Yang, Zhen; Quan, Jing

doi:10.1002/cmdc.202100526

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…DAMP-induced damage can, in turn, generate DAMPs and precipitate self-perpetuating physiologic disarray in injured patients. A variety of potential pharmacological therapeutics exist with the potential to arrest these DAMP-related pathophysiological processes in trauma [ 54 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

Krocker

Lee

Henriksen

et al. 2022

IJMS

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Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. Conclusions: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

Krocker

Lee

Henriksen

et al. 2022

IJMS

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“…4MCsA, an albumin-bound CsA analogue, presents prospective inhibitory effects on chemotactic activity and inflammation by targeting extracellular cyclophilin A. The binding affinity of 4MCsA to cyclophilin A is similar to that of CsA, but lacks immunosuppressive ability and cytotoxicity [ 108 ].…”

Section: Cyclic Peptides As Cyclophilin a Inhibitorsmentioning

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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Protein-mediated fluorescent probes for bioimaging and biosensing: From fundamentals to applications

Yu,

Li,

Wang

et al. 2024

TrAC Trends in Analytical Chemistry

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Targeting Extracellular Cyclophilin A via an Albumin‐Binding Cyclosporine A Analogue

Cited by 3 publications

References 36 publications

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

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

Protein-mediated fluorescent probes for bioimaging and biosensing: From fundamentals to applications

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