| Literature DB >> 29102228 |
Andrew F Donnell1, Yong Zhang2, Erik M Stang2, Donna D Wei2, Andrew J Tebben2, Heidi L Perez2, Gretchen M Schroeder2, Chin Pan3, Chetana Rao3, Robert M Borzilleri2, Gregory D Vite2, Sanjeev Gangwar3.
Abstract
Macrocyclic pyrrolobenzodiazepine dimers were designed and evaluated for use as antibody-drug conjugate payloads. Initial structure-activity exploration established that macrocyclization could increase the potency of PBD dimers compared with non-macrocyclic analogs. Further optimization overcame activity-limiting solubility issues, leading to compounds with highly potent (picomolar) activity against several cancer cell lines. High levels of in vitro potency and specificity were demonstrated with an anti-mesothelin conjugate.Entities:
Keywords: Antibody-drug conjugates; Macrocycles; Pyrrolobenzodiazepines
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Year: 2017 PMID： 29102228 DOI： 10.1016/j.bmcl.2017.10.028
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823