Abstract 2427: Molecular and pharmacokinetic studies of dicycloplatin, a new platinum analogue, suggest it is a promising chemotherapeutic agent.

Abstract

Abstract Dicycloplatin (DCP), a new platinum compound recently approved by the Chinese FDA, is a platinum-based supramolecule. The host-part (carboplatin) and a guest-part (cyclobutane-1,1-dicarboxylic acid or CBDC) are linked by hydrogen bonds. DCP has a stable chemical structure and good water solubility. Pharmacokinetic studies show that the prototype DCP concentration 2-h after administration is still high (17.1 μg/ml), after 26.9 μg/ml at 0.5 hour. In comparison, 5.01 μg/ml of carboplatin prototype is obtained 2-h after administration. Preclinical in vitro and in vivo studies and a phase I clinical trial demonstrated that DCP possesses significant antitumor activity, with fewer adverse effects than carboplatin. Molecular investigation of DCP-treated ovarian cancer A2780 cells showed activation of several kinases, including Chk2, p53, BRCA1 and other downstream factors. The increase in activated p-Chk2, p-p53 and p-BRCA1 after 1-h DCP exposure at IC50 dose occurred in a time-dependent manner. Quantitative analysis of phosphorylated Chk2 and BRCA1 expression revealed that the amount of dicycloplatin-induced phosphorylation of the two factors doubled at 48-h and tripled for p53 at 24-h, compared to controls. We observed that the DCP-induced activation profile and cisplatin-activated mechanisms are similar. We conclude that dicycloplatin is a promising platinum chemotherapeutic compound. Citation Format: Xuqing Yang, Qinhua Song, Michael D. Mueller, Jing Jie Yu. Molecular and pharmacokinetic studies of dicycloplatin, a new platinum analogue, suggest it is a promising chemotherapeutic agent. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2427. doi:10.1158/1538-7445.AM2013-2427