Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer.
Invest New Drugs
; 31(5): 1142-50, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23392775
ABSTRACT
Previously, we reported on the anti-tumor activities of two designed calix[4]arene-based topomimetics (PTX008 and PTX009) of the amphipathic, angiostatic peptide Anginex. Here, we chemically modified the hydrophobic and hydrophilic faces of PTX008 and PTX009, and discovered new calixarene compounds that are more potent, cytotoxic anti-tumor agents. One of them, PTX013, is particularly effective at inhibiting the growth of several human cancer cell lines, as well as drug resistant cancer cells. Mechanistically, PTX013 induces cell cycle arrest in sub-G1 and G0/G1 phases of e.g. SQ20B cells, a radio-resistant human head and neck carcinoma model. In the syngeneic B16F10 melanoma tumor mouse model, PTX013 (0.5 mg/Kg) inhibits tumor growth by about 50-fold better than parent PTX008. A preliminary pharmacodynamics study strongly suggests that PTX013 exhibits good in vivo exposure and a relatively long half-life. Overall, this research contributes to the discovery of novel therapeutics as potentially useful agents against cancer in the clinic.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citotoxinas
/
Calixarenos
/
Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Invest New Drugs
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos