Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer

Ruud P.M. Dings, Joseph I. Levine, Susan G. Brown, Lucile Astorgues-Xerri, John R. MacDonald, Thomas R. Hoye, Eric Raymond, Kevin H. Mayo

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1142-1150
Number of pages9
JournalInvestigational New Drugs
Issue number5
StatePublished - Oct 2013

Bibliographical note

Funding Information:
Acknowledgements This work was supported by research grants from the National institute of Health - National Cancer Institute (CA-096090 and CA-76497) and OncoEthix Inc. to KHM. ER and LA-X were supported by OncoEthix Inc., the Foundation Nelia & Amadeo Barleta (FNAB), and the Association pour la Recherche & l’Enseigne-ment en Cancérologie (AAREC).


  • Calixarenes
  • Galectin-1
  • Structure-Activity relationships
  • Therapeutics


Dive into the research topics of 'Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer'. Together they form a unique fingerprint.

Cite this