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Discovery of novel polyamide-pyrrolobenzodiazepine hybrids for antibody-drug conjugates

Authors :
Joshua D, Thomas
Aleksandr V, Yurkovetskiy
Mao, Yin
Natalya D, Bodyak
Dmitry R, Gumerov
Shuyi, Tang
Eoin, Kelleher
Brian D, Jones
Marina, Protopopova
LiuLiang, Qin
Alex, Uttard
Damon R, Demady
Timothy B, Lowinger
Source :
Bioorganic & Medicinal Chemistry Letters. 72:128876
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Pyrrolobenzodiazepine (PBD) dimers are well-known highly potent antibody drug conjugate (ADC) payloads. The corresponding PBD monomers, in contrast, have received much less attention from the ADC community. We prepared several novel polyamide-linked PBD monomers and evaluated their utility as ADC payloads. The unconjugated polyamide-PBD hybrids exhibited potent antiproliferative activity (IC50 range: 10

Details

ISSN :
0960894X
Volume :
72
Database :
OpenAIRE
Journal :
Bioorganic & Medicinal Chemistry Letters
Accession number :
edsair.doi.dedup.....6c28732d20f05570a4c9c7504b2fae53
Full Text :
https://doi.org/10.1016/j.bmcl.2022.128876