Antagonism of the ATP-gated P2X7 receptor: a potential therapeutic strategy for cancer.
Purinergic Signal
; 17(2): 215-227, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33728582
ABSTRACT
The P2X receptor 7 (P2X7R) is a plasma membrane receptor sensing extracellular ATP associated with a wide variety of cellular functions. It is most commonly expressed on immune cells and is highly upregulated in a number of human cancers where it can play a trophic role in tumorigenesis. Activation of this receptor leads to the formation of a non-selective cation channel, which has been associated with several cellular functions mediated by the PI3K/Akt pathway and protein kinases. Due to its broad range of functions, the receptor represents a potential therapeutic target for a number of cancers. This review describes the range of mechanisms associated with P2X7R activation in cancer settings and highlights the potential of targeted inhibition of P2X7R as a therapy. It also describes in detail a number of key P2X7R antagonists currently in pre-clinical and clinical development, including oxidised ATP, Brilliant Blue G (BBG), KN-62, KN-04, A740003, A438079, GSK1482160, CE-224535, JNJ-54175446, JNJ-55308942, and AZ10606120. Lastly, it summarises the in vivo studies and clinical trials associated with the use and development of these P2X7R antagonists in different disease contexts.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trifosfato de Adenosina
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Receptores Purinérgicos P2X7
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Antagonistas do Receptor Purinérgico P2X
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Neoplasias
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Purinergic Signal
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Austrália