Evaluation of PNU-159682 antibody drug conjugates (ADCs).
PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody drug conjugates (ADCs). Structure activity relationships were explored on the small molecule which led to six linker drugs being developed for conjugation to antibodies. Herein we describe the synthesis of novel PNU-159682 derivatives and the subsequent linker drugs as well as the corresponding biological evaluations of the small molecules and ADCs.
['Holte|Dane|D|', 'Lyssikatos|Joseph P|JP|', 'Valdiosera|Amanda M|AM|', 'Swinney|Zachary|Z|', 'Sisodiya|Vikram|V|', 'Sandoval|Joseph|J|', 'Lee|Christina|C|', 'Aujay|Monette A|MA|', 'Tchelepi|Robert B|RB|', 'Hamdy|Omar M|OM|', 'Gu|Christine|C|', 'Lin|Baiwei|B|', 'Sarvaiya|Hetal|H|', 'Pysz|Marybeth A|MA|', 'Laysang|Amy|A|', 'Williams|Samuel|S|', 'Jun Lee|Dong|D|', 'Holda|Magda K|MK|', 'Purcell|James W|JW|', 'Gavrilyuk|Julia|J|']
D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D004317:Doxorubicin D006801:Humans D018796:Immunoconjugates D016688:Mice, Inbred NOD D016513:Mice, SCID D009369:Neoplasms
PNU-159682 Antibody drug conjugate Nemorubicin Doxorubicin