Significant activity of a novel cytotoxic agent, LY295501, against a wide range of tumors in the human tumor cloning system.
The diarylsulfonylureas (DSUs) are a novel class of cytotoxic agents with high potential for activity. LY295501 is one of the most active DSUs. In this study, we evaluated the cytotoxicity of LY295501 utilizing the human tumor cloning assay. LY295501 was tested at 10, 50 and 100 microg/ml using either 1 h or continuous exposure schedules. The majority of common solid tumors were evaluated including breast, colorectal, non-small cell lung and ovarian carcinomas. LY295501 demonstrated significant activity against all tumor types tested. Antitumor activity was noted after either 1 h or continuous exposure schedules at all concentrations tested. A concentration-response relationship was noted, with increasing concentrations of LY295501 leading to more cytotoxicity. Cytotoxicity, on the continuous exposure schedule, was noted in 38% of tumors exposed to LY295501 at 10 microg/ml, 58% of tumors exposed at 50 microg/ml (p=0.002 for 10 versus 50 microg/ml) and 72% of tumors exposed at 100 microg/ml (p=0.008 for 50 versus 100 microg/ml). In addition, more cytotoxicity was observed on the continuous exposure schedule compared to the 1 h schedule at all concentrations tested (p<0.01). The substantial activity of LY295501 in the human tumor cloning assay coupled with its clinical activity in phase I studies supports further clinical development of this agent.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010671:Phenylurea Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured