Ingenane Diterpenoids from Euphorbia peplus as Potential New CHK1 Inhibitors That Sensitize Cancer Cells to Chemotherapy DOI
Mi Zhou,

Yanlan Yang,

Shoulun He

и другие.

Journal of Natural Products, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Phosphorylation of checkpoint kinase 1 at Ser-345 (p-CHK1(S345)) mediates the replication stress response in cancer cells, leading to chemotherapy resistance. Therefore, finding inhibitors p-CHK1(S345) is currently a promising strategy prevent acquired drug In this study, 14 ingenane diterpenoids (1-14), involving two undescribed compounds possessing an unprecedented exocyclic double bond Δ6(20), were identified from Euphorbia peplus. The inhibitory effects isolated on and their structure-activity relationship (SAR) investigated. Compounds 7 8 presented strongest effects, abrogated cell cycle arrest, caused accumulation DNA damage, improving sensitivity cells chemotherapeutic drugs. An vivo assay confirmed enhancement anticancer effect topotecan via blocking p-CHK1(S345). Mechanistically, increased CHK1 ubiquitination inhibit activation protein C (PKC). PKC was first found enhance block Above all, not only indicates that compound could be developed as novel inhibitor but also reveals previously unrecognized role regulating sensitivity.

Язык: Английский

Macrolide sesquiterpene pyridine alkaloids from the roots of Tripterygium regelii and their anti-inflammatory activity DOI
Dawei Li, Qi Jia, Qi Zhao

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер 158, С. 108330 - 108330

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Ingenane Diterpenoids from Euphorbia peplus as Potential New CHK1 Inhibitors That Sensitize Cancer Cells to Chemotherapy DOI
Mi Zhou,

Yanlan Yang,

Shoulun He

и другие.

Journal of Natural Products, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Phosphorylation of checkpoint kinase 1 at Ser-345 (p-CHK1(S345)) mediates the replication stress response in cancer cells, leading to chemotherapy resistance. Therefore, finding inhibitors p-CHK1(S345) is currently a promising strategy prevent acquired drug In this study, 14 ingenane diterpenoids (1-14), involving two undescribed compounds possessing an unprecedented exocyclic double bond Δ6(20), were identified from Euphorbia peplus. The inhibitory effects isolated on and their structure-activity relationship (SAR) investigated. Compounds 7 8 presented strongest effects, abrogated cell cycle arrest, caused accumulation DNA damage, improving sensitivity cells chemotherapeutic drugs. An vivo assay confirmed enhancement anticancer effect topotecan via blocking p-CHK1(S345). Mechanistically, increased CHK1 ubiquitination inhibit activation protein C (PKC). PKC was first found enhance block Above all, not only indicates that compound could be developed as novel inhibitor but also reveals previously unrecognized role regulating sensitivity.

Язык: Английский

Процитировано

0