Evaluation of PNU-159682 antibody drug conjugates (ADCs).
Basic Information
ID: ALA4673263
Journal: Bioorg Med Chem Lett
Title: Evaluation of PNU-159682 antibody drug conjugates (ADCs).
Authors: Holte D,Lyssikatos JP,Valdiosera AM,Swinney Z,Sisodiya V,Sandoval J,Lee C,Aujay MA,Tchelepi RB,Hamdy OM,Gu C,Lin B,Sarvaiya H,Pysz MA,Laysang A,Williams S,Jun Lee D,Holda MK,Purcell JW,Gavrilyuk J
Abstract: 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.
CiteXplore: 33127540
DOI: 10.1016/j.bmcl.2020.127640
Patent ID: ┄