Discovery of novel antitumor sulfonamides targeting G1 phase of the cell cycle

Described herein is the discovery of a novel series of antitumor sulfonamid es targeting G1 phase of the cell cycle. Cell cycle control in G1 phase has attracted considerable attention in recent cancer research, because many o f the important proteins involved in G1 progression or G1/S transition have been found to play a crucial role in proliferation, differentiation, trans formation, and programmed cell death (apoptosis). We previously reported ou r first antitumor sulfonamide E7010 as a novel tubulin polymerization inhib itor. Interestingly enough, continuous research on structurally related com pounds led us to the finding of another class of antitumor sulfonamides tha t block cell cycle progression of P388 murine leukemia cells in GI phase, b ut not in M phase. Of the compounds examined, N-(3-chloro-7-indolyl)-1,4-be nzenedisulfonamide (E7070) showed significant antitumor activity against HC T116 human colon carcinoma both in vitro (IC50 0.11 mu g/mL in cell prolife ration assay) and in vivo (not only growth suppression but also a marked re duction of tumor size in nude mice). Because of its promising efficacy agai nst human tumor xenografts and its unique mode of action, E7070 is currentl y undergoing phase I clinical trials in European countries.