[PMID]: | 28416275 |
[Au] Autor: | Nath AK; Shi X; Harrison DL; Morningstar JE; Mahon S; Chan A; Sips P; Lee J; MacRae CA; Boss GR; Brenner M; Gerszten RE; Peterson RT |
[Ad] Endereço: | Division of Cardiology, Department of Medicine, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA. Electronic address: anjali.nath@aya.yal |
[Ti] Título: | Cisplatin Analogs Confer Protection against Cyanide Poisoning. |
[So] Source: | Cell Chem Biol;24(5):565-575.e4, 2017 May 18. |
[Is] ISSN: | 2451-9456 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in cyanide detoxification in vivo. Cyanide kills organisms as diverse as insects, fish, and humans within seconds to hours. Current antidotes exhibit limited efficacy and are not amenable to mass distribution requiring the development of new classes of antidotes. The binding affinity of the cyanide anion for the positively charged metal platinum is known to create an extremely stable complex in vitro. We therefore screened a panel of diverse cisplatin analogs and identified compounds that conferred protection from cyanide poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery pipeline begins to establish the characteristics of platinum ligands that influence their solubility, toxicity, and efficacy, and provides proof of concept that platinum-based complexes are effective antidotes for cyanide poisoning. |
[Mh] Termos MeSH primário: |
Antídotos/química Antídotos/farmacologia Cisplatino/análogos & derivados Cisplatino/farmacologia Cianetos/envenenamento
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[Mh] Termos MeSH secundário: |
Animais Antídotos/metabolismo Linhagem Celular Cisplatino/metabolismo Cianetos/química Cianetos/metabolismo Aprovação de Drogas Complexo IV da Cadeia de Transporte de Elétrons/metabolismo Seres Humanos Dose Letal Mediana Oxirredução/efeitos dos fármacos Coelhos Solubilidade Enxofre/química Peixe-Zebra
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antidotes); 0 (Cyanides); 70FD1KFU70 (Sulfur); EC 1.9.3.1 (Electron Transport Complex IV); Q20Q21Q62J (Cisplatin) |
[Em] Mês de entrada: | 1707 |
[Cu] Atualização por classe: | 170707 |
[Lr] Data última revisão:
| 170707 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170419 |
[St] Status: | MEDLINE |
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