RT Journal Article
T1 Zaltoprofen and its novel analogues exhibit dual targeting of COX-2 and PPAR-γ, providing a strategy to alleviate lipopolysaccharide – induced acute lung injury.
A1 Lu, Qirong
A1 Zhao, Yongxia
A1 Xu, Xiaoqing
A1 Guo, Pu
A1 Ares Lombán, Irma
A1 Martínez Caballero, Marta
A1 López Torres, Bernardo
A1 Martínez Larrañaga, María Rosa
A1 Anadón Navarro, Arturo Ramón
A1 Pan, Yuanhu
A1 Wang, Xu
A1 Martínez Caballero, María Aranzazu
AB Acute lung injury (ALI) is a multi-system and multifactorial disease, which is characterised by an uncontrolled inflammatory response and high mortality. Zaltoprofen (ZPF), is a non-steroidal anti-inflammatory drug (NSAID) with powerful anti-inflammatory effects, as well as an analgesic action on inflammatory pain. Therefore, this research study aims to explore whether ZPF, its main metabolite M2 (S-oxide-zaltoprofen) and novel analogues can alleviate ALI through multiple targets. Based on molecular docking, the similar topological structure binding properties of protein targets (STSBPT) strategy, the cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS), for first time, this study found that cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-γ (PPAR-γ) are dual targets of ZPF and M2. Based on this outcome, novel analogues related to ZPF and M2 were designed. The present research study also examined the effect and the cellular and molecular mechanisms of ZPF, M2 and the novel analogues on LPS-induced ALI in vitro and in vivo, through the dual targets of COX-2 and PPAR-γ. The findings of this study suggest that the STSBPT strategy could assist as a probable multi-target medicinal drug screening strategy, and ZPF, its main metabolite M2 and its novel analogues could serve as potential therapeutic agents for the treatment of ALI, through the both COX-2 and PPAR-γ molecular signalling targets.
PB Elsevier Inc.
SN 0006-2952
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/125071
UL https://hdl.handle.net/20.500.14352/125071
LA eng
NO Lu, Q., Zhao, Y., Xu, X., Guo, P., Ares, I., Martínez, M., Lopez-Torres, B., Martínez-Larrañaga, M.-R., Anadón, A., Pan, Y., Wang, X., & Martínez, M.-A. (2025). Zaltoprofen and its novel analogues exhibit dual targeting of COX-2 and PPAR-γ, providing a strategy to alleviate lipopolysaccharide – induced acute lung injury. Biochemical Pharmacology, 242, 117420. https://doi.org/10.1016/j.bcp.2025.117420
NO CRediT authorship contribution statement Qirong Lu: Writing – review & editing, Formal analysis, Methodology, Data curation, Investigation. Yongxia Zhao: Investigation, Writing – review & editing, Formal analysis, Methodology, Data curation. Xiaoqing Xu: Methodology, Data curation, Investigation, Writing – review & editing, Formal analysis. Pu Guo: Writing – review & editing, Formal analysis, Methodology, Data curation, Investigation. Irma Ares: Investigation, Writing – review & editing, Formal analysis, Methodology, Data curation. Marta Martínez: Methodology, Data curation, Investigation, Writing – review & editing, Formal analysis. Bernardo Lopez-Torres: Writing – review & editing, Formal analysis, Methodology, Data curation, Investigation. María-Rosa Martínez-Larranaga: ˜ Investigation, Writing – review & editing, Formal analysis, Methodology, Data curation. Arturo Anadon: ´ Writing – review & editing, Funding acquisition, Conceptualization, Writing – original draft, Formal analysis, Project administration, Data curation. Yuanhu Pan: Writing – original draft, Formal analysis, Project administration, Data curation, Writing – review & editing, Funding acquisition, Conceptualization. Xu Wang: Project administration, Data curation, Writing – review & editing, Funding acquisition, Conceptualization, Writing – original draft, Formal analysis. María-Aranzazu ´ Martínez: Project administration, Data curation, Writing – review & editing, Funding acquisition, Conceptualization, Writing – original draft, Formal analysis.
NO Ministerio de Ciencia e Innovación (España)
NO National Natural Science Foundation (China)
NO Programa Nacional de Investigación y Desarrollo Clave de China
NO Programa Nacional de Investigación y Desarrollo Clave de China
DS Docta Complutense
RD 19 oct 2025