DpC

DpC is a selective, orally active iron chelator with anticancer activity. DpC acts on signaling pathway-related targets such as JNK, NF-κB, and its activity is competitively inhibited by another iron chelator Dp44mT (HY-18973). By chelating intracellular iron and copper ions in tumor cells to form redox-active complexes, DpC induces oxidative stress, activates the JNK, NF-κB pathways and downregulates IκBα, upregulates the expressions of neuroglobin and cytoglobin, activates caspase 3/9 to induce tumor cell apoptosis. It also overcomes P-glycoprotein-mediated multidrug resistance through a lysosome-targeting mechanism, and exhibits broad-spectrum synergistic effects when combined with various chemotherapeutic agents. DpC inhibits tumor metastasis and increases TNF-α levels in the tumor microenvironment to enhance endogenous immune responses. DpC is applicable to the research of various malignancies including neuroblastoma, pancreatic cancer, prostate cancer, lung cancer, and breast cancer^[1][2][3]. In Vitro:DpC (24 h; 72 h) exhibits potent and selective antiproliferative activity against PANC-1, PC3, DMS-53, DU-145 and MDA-MB-231 tumor cells. Meanwhile, it produces synergistic effects in combination with 9 clinical chemotherapeutic agents including Abiraterone (HY-70013), Carboplatin (HY-17393), Cisplatin (HY-17394) and Doxorubicin (HY-15142), but shows antagonistic effects when combined with Dp44mT^[1].
Uptake of ¹⁴C-DpC (25 μM; 2 h) by SK-N-MC neuroepithelioma cells depends on temperature- and energy-dependent regulatory mechanisms, and DpC competes with Dp44mT for the same cellular uptake carrier/receptor^[1].
DpC (25 μM; 24 h) exhibits antiproliferative activity against MSC, H9C2, MIHA, HK2 and SK-N-LP cells, with significantly higher activity in SK-N-LP cells than Dp44mT and L1. It also significantly upregulates the expressions of neuroglobin (Ngb) and cytoglobin (Cygb) in SK-N-LP and HK2 cells, increases the levels of phosphorylated JNK, cleaved caspase 3 and cleaved caspase 9, and decreases the level of IkBα^[2]. In Vivo:DpC (4 mg/kg; tail vein injection; once daily; 3 weeks) significantly reduces tumor imaging ROI values and tumor volumes, increases the levels of Annexin V (+)/PI (+) cells, caspase 3, neuroglobin, cytoglobin and TNFα, slightly decreases IL-10 levels in tumor tissues, slightly inhibits body weight gain of mice, and does not cause obvious toxicity but induces pulmonary exudative inflammation in an orthotopic SK-N-LP/Luciferase neuroblastoma xenograft model in the left adrenal fat pad of nude mice^[2].