Chemical Modification of Linkers Provides Stable Linker-Payloads for the Generation of Antibody-Drug Conjugates.
ACS Med Chem Lett
; 11(11): 2190-2194, 2020 Nov 12.
Article
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| MEDLINE
| ID: mdl-33214828
ABSTRACT
Stability of antibody-drug conjugates (ADCs) in mouse serum is one of the critical requirements for the evaluation of ADCs in mouse tumor models. Described herein is a strategy to address the mouse serum instability of uncialamycin linker-payloads through various chemical approaches that involve modification of different parts of the linker and payload. This effort ultimately led to the identification of a m-amide p-aminobenzyl carbamate (MA-PABC) group that resulted in linkers with dramatic improvement of mouse serum stability without affecting the desired proteolytic cleavage.
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Base de datos:
MEDLINE
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En
Revista:
ACS Med Chem Lett
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos