气候变化领域集成服务门户(CCPortal): Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth

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DOI	10.1073/pnas.2025806118
	Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth
	Wan P.-K.; Tong K.-C.; Lok C.-N.; Zhang C.; Chang X.-Y.; Sze K.-H.; Tsai Wong A.S.; Che C.-M.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Vimentin is a cytoskeletal intermediate filament protein that plays pivotal roles in tumor initiation, progression, and metastasis, and its overexpression in aggressive cancers predicted poor prognosis. Herein described is a highly effective antitumor and antimetastatic metal complex [PtII(C^N^N)(NHC2Bu)]PF6 (Pt1a; HC^N^N = 6-phenyl-2,2′-bipyridine; NHC= N-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 μM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)-NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antimetastasis; Metabolism; N-heterocyclic carbene; Platinum; Vimentin
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179758
作者单位	State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong, Hong Kong; Laboratory for Synthetic Chemistry and Chemical Biology, Hong Kong, Hong Kong; Department of Chemistry, Southern University of Science and Technology of China, Shenzhen, Guangdong, 518055, China; Department of Microbiology, The University of Hong Kong, Hong Kong, Hong Kong; School of Biological Sciences, The University of Hong Kong, Hong Kong, Hong Kong
推荐引用方式 GB/T 7714	Wan P.-K.,Tong K.-C.,Lok C.-N.,et al. Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth[J],2021,118(17).
APA	Wan P.-K..,Tong K.-C..,Lok C.-N..,Zhang C..,Chang X.-Y..,...&Che C.-M..(2021).Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Wan P.-K.,et al."Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).