Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer.
Invest New Drugs
; 31(5): 1142-50, 2013 Oct.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytotoxins
/
Calixarenes
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Invest New Drugs
Year:
2013
Type:
Article
Affiliation country:
United States