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Hydrophilic Monomethyl Auristatin E Derivatives as Novel Candidates for the Design of Antibody-Drug Conjugates

1
Department of Chemistry, University of Helsinki, PO Box 55, A. I. Virtasen aukio 1, FI 00014 Helsinki, Finland
2
Glykos Finland Ltd., Viikinkaari 6, 00790 Helsinki, Finland
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Separations 2019, 6(1), 1; https://doi.org/10.3390/separations6010001
Received: 28 October 2018 / Revised: 6 December 2018 / Accepted: 14 December 2018 / Published: 24 December 2018
(This article belongs to the Special Issue Five Years of Separations: Feature Paper 2018)
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Abstract

Antibody-drug conjugates (ADCs) are promising state-of-the-art biopharmaceutical drugs for selective drug-delivery applications and the treatment of diseases such as cancer. The idea behind the ADC technology is remarkable as it combines the highly selective targeting capacity of monoclonal antibodies with the cancer-killing ability of potent cytotoxic agents. The continuous development of improved ADCs requires systematic studies on the nature and effects of warhead modification. Recently, we focused on the hydrophilic modification of monomethyl auristatin E (MMAE), the most widely used cytotoxic agent in current clinical trial ADCs. Herein, we report on the use of micellar electrokinetic chromatography (MEKC) for studying the hydrophobic character of modified MMAE derivatives. Our data reveal a connection between the hydrophobicity of the modified warheads as free molecules and their cytotoxic activity. In addition, MMAE-trastuzumab ADCs were constructed and evaluated in preliminary cytotoxic assays. View Full-Text
Keywords: antibody-drug conjugate; biopharmaceutical; cytotoxicity; hydrophobicity; micellar electrokinetic chromatography antibody-drug conjugate; biopharmaceutical; cytotoxicity; hydrophobicity; micellar electrokinetic chromatography
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Ekholm, F.S.; Ruokonen, S.-K.; Redón, M.; Pitkänen, V.; Vilkman, A.; Saarinen, J.; Helin, J.; Satomaa, T.; Wiedmer, S.K. Hydrophilic Monomethyl Auristatin E Derivatives as Novel Candidates for the Design of Antibody-Drug Conjugates. Separations 2019, 6, 1.

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