Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 남태규 | - |
dc.date.accessioned | 2023-04-25T04:12:47Z | - |
dc.date.available | 2023-04-25T04:12:47Z | - |
dc.date.issued | 2023-05 | - |
dc.identifier.citation | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 251.0, article no. 115274, | en_US |
dc.identifier.issn | 0223-5234;1768-3254 | en_US |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0223523423002404?via%3Dihub | en_US |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/179295 | - |
dc.description.abstract | In this study, a new series of 3-arylidene-4,6-dimethyl-5-hydroxy-7-azaoxindole compounds with a wide range of functional groups were designed, synthesized, and evaluated for their antitumor activity. Among the 35 com-pounds, compound 6-15, with a quinoline moiety, showed cytotoxic IC50 values superior to those of sunitinib against the seven cancer cell lines (MCF-7, MDA-MB-231, HT-29, DU145, U937, A549, and PANC-1). However, its inhibitory activity against receptor tyrosine kinases (VEGFR2, PDGFR beta, c-KIT, FGFR1, FLT3, CSF1R, EGFR, Axl, and Axl mutant) was 100 -3000-fold weaker than that of sunitinib. Interestingly, compound 6-15 exerted a 3.6-fold stronger cytotoxicity than sunitinib in the gemcitabine-resistant PANC-1 cell line and significantly inhibited Axl, which was in contrast with the effect of sunitinib. Nonetheless, both compounds suppressed the expression of growth arrest-specific 6 (Gas6), the ligand of Axl. The inhibitory effect of compound 6-15 on the Gas6-Axl axis was similar to that of Gas6 knockdown by siRNA in PANC-1 cells in terms of apoptosis induction, increase in Bax/Bcl-2 ratio, Axl down-regulation, and PI3K/Akt inhibition. The inhibitory effect of compound 6-15 on tumor growth in mouse tumor models with A549 and PANC-1 xenografts was much greater than that of cisplatin or gemcitabine. Taken together, the current findings demonstrate that compound 6-15 is a promising anticancer drug candidate that acts by inhibiting the Gas6-Axl axis. | - |
dc.description.sponsorship | Acknowledgements This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (Grant No.: NRF-2018R1A2B6001299 and NRF-2020R1A2C2005690) . | - |
dc.language | en | en_US |
dc.publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | en_US |
dc.subject | 7-Azaoxindole | - |
dc.subject | Gas6 | - |
dc.subject | Axl | - |
dc.subject | TAM family Receptor tyrosine kinase | - |
dc.subject | Apoptosis | - |
dc.subject | Bax | - |
dc.subject | Bcl-2 | - |
dc.title | Antitumor effect of 3-(quinolin-2-ylmethylene)-4,6-dimethyl-5-hydroxy-7-azaoxindole down-regulating the Gas6-Axl axis | en_US |
dc.type | Article | en_US |
dc.relation.volume | 251.0 | - |
dc.identifier.doi | 10.1016/j.ejmech.2023.115274 | en_US |
dc.relation.journal | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.contributor.googleauthor | Bae, Dawon | - |
dc.contributor.googleauthor | Chaudhary, Prakash | - |
dc.contributor.googleauthor | Been, Jae-Hui | - |
dc.contributor.googleauthor | Gautam, Jaya | - |
dc.contributor.googleauthor | Lee, Jisu | - |
dc.contributor.googleauthor | Shah, Sajita | - |
dc.contributor.googleauthor | Kim, Euijung | - |
dc.contributor.googleauthor | Lee, Hyunji | - |
dc.contributor.googleauthor | Nam, Tae-gyu | - |
dc.contributor.googleauthor | Jeong, Byeong-Seon | - |
dc.contributor.googleauthor | Kim, Jung-Ae | - |
dc.sector.campus | E | - |
dc.sector.daehak | 약학대학 | - |
dc.sector.department | 약학과 | - |
dc.identifier.pid | tnam | - |
dc.identifier.article | 115274 | - |
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