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

Yanlan Yang,

Shoulun He

et al.

Journal of Natural Products, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

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

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 158, P. 108330 - 108330

Published: March 1, 2025

Language: Английский

Citations

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

Yanlan Yang,

Shoulun He

et al.

Journal of Natural Products, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

0