Hu, Di; Yang, Chen; Lok, Chun-Nam; Xing, Fangrong; Lee, Pui-Yan; Fung, Yi Man Eva; Jiang, Haibo; Che, Chi-Ming published the article 《An Antitumor Bis(N-Heterocyclic Carbene)Platinum(II) Complex That Engages Asparagine Synthetase as an Anticancer Target》. Keywords: platinum heterocyclic carbene synthesis anticancer asparagine synthetase proteome; N-heterocyclic carbenes; antitumor agents; asparagine synthetase; platinum complexes; thermal proteome profiling.They researched the compound: Dichloro(1,5-cyclooctadiene)platinum(II)( cas:12080-32-9 ).Name: Dichloro(1,5-cyclooctadiene)platinum(II). Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:12080-32-9) here.
New anticancer platinum(II) compounds with distinctive modes of action are appealing alternatives to combat the drug resistance and improve the efficacy of clin. used platinum chemotherapy. Herein, we describe a rare example of an antitumor PtII complex targeting a tumor-associated protein, rather than DNA, under cellular conditions. Complex [(bis-NHC)Pt(bt)]PF6 (1a; Hbt=1-(3-hydroxybenzo[b]thiophen-2-yl)ethanone) overcomes cisplatin resistance in cancer cells and displays significant tumor growth inhibition in mice with higher tolerable doses compared to cisplatin. The cellular Pt species shows little association with DNA, and localizes in the cytoplasm as revealed by nanoscale secondary ion mass spectrometry. An unbiased thermal proteome profiling experiment identified asparagine synthetase (ASNS) as a mol. target of 1a. Accordingly, 1a treatment reduced the cellular asparagine levels and inhibited cancer cell proliferation, which could be reversed by asparagine supplementation. A bis-NHC-ligated Pt species generated from the hydrolysis of 1 a forms adducts with thiols and appears to target an active-site cysteine of ASNS.
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