SU-DHL-6

In Vitro Antitumour Efficacy of an Injectable Formulation of Purinostat Mesylate in SU-DHL-6 Tumour Model

Purinostat Mesylate (PM) has emerged as a powerful new inhibitor of HDAC with antitumor properties according to existing research. However, due to its low water solubility and bioavailability, it hinders its clinical development. In the present work, a PM/HP-β-CD inclusion complex was prepared and characterized. Its antitumor effect was demonstrated via in vitro cytotoxicity and apoptosis assays, in vitro and in vivo pharmacokinetic studies. Flow cytometry was utilized to research the apoptosis process in SU-DHL-6 cells. As demonstrated in Figures 1A-B, when treated with 6 nM LBH589, 3 nM PM, 6 nM PM and PM/HP-β-CD for 48 h, the apoptosis rate was 60.1%, 14.99%, 55.2%, 21.18% and 66%, respectively. PM/HP-β-CD was slightly better than PM in terms of apoptosis induction. As shown in Figure 1C, HP-β-CD alone did not show cytotoxicity within the range of 799.6 nM (mean survival rate: 100.85%), and PM and PM/HP-β-CD had a dose-dependent inhibitory effect on cell proliferation with IC₅₀ values of 1.88 nM and 2.43 nM, respectively.

Fig. 1. In vitro antitumour effect of PM/HP-β-CD inclusion complex (Zhu Z J, Wen J L, et al., 2022).

ZY0511 Inhibits the Proliferation of DLBCL Cells

Lysine-specific demethylase 1 (LSD1/KDM1A) is a promising therapeutic target in cancer, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. Studies show that KDM1A is overexpressed in DLBCL and correlates with poor patient survival. In this study, Liu's team explored the anti-tumor activity of ZY0511, a novel LSD1 inhibitor, on DLBCL. To evaluate the impact of ZY0511 on DLBCL cells, MTT assay was conducted and found ZY0511 exerted an anti-proliferation effect on SU-DHL-4, SU-DHL-6, SU-DHL-10 and Farage cells in a dose- and time-dependent manner (IC₅₀: 0.33–2.87 μM; Fig. 2c). SU-DHL-4 and SU-DHL-6 cells were the most sensitive to ZY0511, and their IC₅₀ values were decreased from 1.57/1.08 μM (24 h) to 0.46/0.39 μM (96 h). The assay results further confirmed that ZY0511 markedly suppressed DNA synthesis, reducing the proportion of cells undergoing active replication from 61.61 to 10.25% in SU-DHL-4, 47.00 to 9.30% in SU-DHL-6, and 52.76 to 12.23% in Farage cells (Fig. 2d). These data showed ZY0511 inhibited cell proliferation in a concentration-dependent manner.

Fig. 2. ZY0511 inhibits DLBCL cells proliferation and interacts with LSD1 in DLBCL Cells (Liu H, Wei J, et al., 2021).