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Evaluation of PNU-159682 antibody drug conjugates (ADCs).

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

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

doi

10.1016/j.bmcl.2020.127640

subject

Has Abstract

pub_date

2020-12-15 00:00:00

pages

127640

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30751-4

journal_volume

30

pub_type

杂志文章

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