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The second\u2010generation of clinically approved antibody\u2013drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide\u2010type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. 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