Supplementary Figures and Table Legends from Small molecules targeting histone H4 as potential therapeutics for chronic myelogenous leukemia

Supplementary Figures and Table from Small molecules targeting histone H4 as potential therapeutics for chronic myelogenous leukemia

<div>Abstract<p>We recently identified a polyamide-chlorambucil conjugate, 1R-Chl, which alkylates and down-regulates transcription of the human histone <i>H4c</i> gene and inhibits the growth of several cancer cell lines <i>in vitro</i> and in a murine SW620 xenograft model, without apparent animal toxicity. In this study, we analyzed the effects of 1R-Chl in the chronic myelogenous leukemia cell line K562 and identified another polyamide conjugate, 6R-Chl, which targets H4 genes and elicits a similar cellular response. Other polyamide conjugates that do not target the <i>H4</i> gene do not elicit this response. In a murine model, both 1R-Chl and 6R-Chl were found to be highly effective in blocking K562 xenograft growth with high-dose tolerance. Unlike conventional and distamycin-based alkylators, little or no cytotoxicities and animal toxicities were observed in mg/kg dosage ranges. These results suggest that these polyamide alkylators may be a viable treatment alternative for chronic myelogenous leukemia. [Mol Cancer Ther 2008;7(4):769–78]</p></div>

<div>Abstract<p>We recently identified a polyamide-chlorambucil conjugate, 1R-Chl, which alkylates and down-regulates transcription of the human histone <i>H4c</i> gene and inhibits the growth of several cancer cell lines <i>in vitro</i> and in a murine SW620 xenograft model, without apparent animal toxicity. In this study, we analyzed the effects of 1R-Chl in the chronic myelogenous leukemia cell line K562 and identified another polyamide conjugate, 6R-Chl, which targets H4 genes and elicits a similar cellular response. Other polyamide conjugates that do not target the <i>H4</i> gene do not elicit this response. In a murine model, both 1R-Chl and 6R-Chl were found to be highly effective in blocking K562 xenograft growth with high-dose tolerance. Unlike conventional and distamycin-based alkylators, little or no cytotoxicities and animal toxicities were observed in mg/kg dosage ranges. These results suggest that these polyamide alkylators may be a viable treatment alternative for chronic myelogenous leukemia. [Mol Cancer Ther 2008;7(4):769–78]</p></div>

Supplementary Figures and Table from Small molecules targeting histone H4 as potential therapeutics for chronic myelogenous leukemia