Jenna H Burton, Christina Mazcko, Amy LeBlanc, Joseph M Covey, Jiuping Ji, Robert J Kinders, Ralph E Parchment, Chand Khanna, Melissa Paoloni, Sue Lana, Kristen Weishaar, Cheryl London, William Kisseberth, Erika Krick, David Vail, Michael Childress, Jeffrey N Bryan, Lisa Barber, E J Ehrhart, Michael Kent, Timothy Fan, Kelvin Kow, Nicole Northup, Heather Wilson-Robles, Joseph Tomaszewski, Julianne L Holleran, Miguel Muzzio, Julie Eiseman, Jan H Beumer, James H Doroshow, Yves Pommier
PURPOSE: Only one chemical class of topoisomerase I (TOP1) inhibitors is FDA approved, the camptothecins with irinotecan and topotecan widely used. Because of their limitations (chemical instability, drug efflux-mediated resistance, and diarrhea), novel TOP1 inhibitors are warranted. Indenoisoquinoline non-camptothecin topoisomerase I (TOP1) inhibitors overcome chemical instability and drug resistance that limit camptothecin use. Three indenoisoquinolines, LMP400 (indotecan), LMP776 (indimitecan), and LMP744, were examined in a phase I study for lymphoma-bearing dogs to evaluate differential efficacy, pharmacodynamics, toxicology, and pharmacokinetics...
December 1, 2018: Clinical Cancer Research