title: E7070: a novel synthetic sulfonamide targeting the cell cycle progression for the treatment of cancer.
abstract: Cell cycle regulation and cell growth are interesting targets in the search for new antitumor agents as these processes are highly disturbed in malignant cells. E7070 is a novel synthetic sulfon-amide that targets the G1 phase of the cell cycle and is currently in clinical development for the treatment of solid tumors. The potential antitumor activity of the compound was discovered through optimization of the structure-activity relationships of a series of sulfonamide structures. E7070 causes a blockade in the G1/S transition through inhibition of the activation of both cyclin-dependent kinase 2 and cyclin E. Preclinical studies with E7070 showed activity in multiple tumor types, most prominently in colon and lung cancer. A phase I clinical program was conducted with E7070 evaluating different treatment regimens. Dose-limiting toxicities were hematological, including neutropenia and thrombocytopenia. Preliminary results of phase II studies demonstrated limited antitumor activity following treatment with E7070 as single agent in heavily pretreated patients with non-small cell lung and colon cancer. Studies evaluating the activity of E7070 in combination with other chemotherapeutic agents are being conducted.
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, Amsterdam, The Netherlands. c.vankesteren@apoth.azu.nl
authors.forename: Charlotte
authors.initials: C
authors.lastname: Van Kesteren
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C439829:N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide; D013449:Sulfonamides