E7070, a novel sulphonamide agent with potent antitumour activity in vitroand in vivo

E7070 (N-(3-Chloro-7-indolyl)-1,4-benzenedisulphonamide) was selected from our sulphonamide compound collections via antitumour screening and flow cyt ometric analysis. Following treatment with E7070, the cell cycle progressio n of P388 murine leukaemia cells was disturbed in the G I phase. The cell-k illing effect on human colon cancer HCT116 cells was found to be time-depen dent. In the panel of 42 human tumour cell lines, E7070 showed an antitumou r spectrum that was distinct from those of other anticancer drugs used in c linic. Animal tests using human tumour xenograft models demonstrated that E 7070 could cause not only tumour growth suppression, but also tumour regres sion in three of five colorectal and two of two lung cancers. In the HCT116 xenograft model, E7070 was shown to be superior to 5-FU, MMC and CPT-11 (i rinotecan). Furthermore, complete regression of advanced LVI tumours was ob served in 80% of E7070-treated mice. All of these observations have promote d this drug to clinical evaluation. (C) 2001 Elsevier Science Ltd. All righ ts reserved.