Hydrophilic Monomethyl Auristatin E Derivatives as Novel Candidates for the Design of Antibody-Drug Conjugates
| Autor: | Tero Satomaa, Filip S. Ekholm, Marina Redón, Virve Pitkänen, Susanne K. Wiedmer, Juhani Saarinen, Jari Helin, Anja Vilkman, Suvi-Katriina Ruokonen |
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| Přispěvatelé: | University of Helsinki, Department, University of Helsinki, Department of Chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Antibody-drug conjugate medicine.drug_class media_common.quotation_subject education 116 Chemical sciences Filtration and Separation Monoclonal antibody biopharmaceutical Micellar electrokinetic chromatography Analytical Chemistry antibody-drug conjugate lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound medicine micellar electrokinetic chromatography Cytotoxicity media_common hydrophobicity Chemistry Combinatorial chemistry lcsh:QC1-999 3. Good health body regions 030104 developmental biology Biopharmaceutical Monomethyl auristatin E lcsh:QD1-999 cytotoxicity lcsh:Physics Conjugate |
| Zdroj: | Separations, Vol 6, Iss 1, p 1 (2018) Separations Volume 6 Issue 1 |
| ISSN: | 2297-8739 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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