For many years, the maleimide–thiol reaction has been the standard method for generating antibody–drug conjugates (ADCs). While efficient and widely used, this chemistry comes with well-known drawbacks—particularly the retro-Michael reaction, which can trigger premature payload release and increase off-target toxicity.

At SigutLabs, we specialize in designing and synthesizing advanced linker–payload systems that address these limitations while preserving thiol selectivity. Our work focuses on alternative electrophilic warheads that deliver improved stability, performance, and adaptability for next-generation ADCs.

Advanced Electrophilic Warheads We Develop

Over time, our chemistry team has synthesized and optimized a broad range of electrophilic linker motifs, including:

• Modified maleimides
  Engineered to accelerate hydrolysis, prevent retro-Michael rearrangements, and maintain strong reactivity.

• N-Methyl-N-phenylvinylsulfonamide
  A well-balanced electrophile combining thiol selectivity with excellent stability.

• Arylpropiolonitrile
  A robust, versatile scaffold suitable for diverse ADC designs.

• 2-Methyl(sulfonyl)pyrimidine
  An emerging electrophile offering strong chemoselectivity for thiol conjugation.

• Custom-designed electrophiles
  Tailored to meet specific stability, reactivity, or payload requirements.

Supporting Your Next ADC Innovation

Whether your goal is a more stable linker–payload connection or exploration of entirely new conjugation chemistries, our team can help you identify and synthesize the right warhead to elevate your ADC program.

Let’s discuss how SigutLabs can support your next project.