We’re researching ADCs with a focus on both ends of bifunctional linkers
To develop next-generation ADCs, our scientists are committed to finding the right chemistry
October 15, 2026
What are antibody-drug conjugates (ADCs)?
Antibody-drug conjugates (ADCs) are a class of drugs designed to deliver a cancer-killing drug to tumor cells while reducing harm to normal or healthy cells. They work by binding to a target expressed on a tumor cell and then delivering its payload once it arrives. For years, much of ADC research and development has centered on finding the right antibody and the right payload to treat a variety of different tumor types.
But the linker that connects the two plays a critical role in how safely and effectively ADCs perform — and optimizing that linker is a complex chemistry problem that requires finding the right balance between stability in circulation and payload release at the target cell.
Every ADC contains three main parts:
- An antibody that helps target specific cells
- A payload that carries the cancer-fighting therapy
- A linker that connects the two and controls payload release
What is a linker in an ADC?
A linker is a specialized chemical connector that attaches to an antibody at one end and a cancer-fighting payload on the other.
The bifunctional linkers do more than connect the antibody and payload; they help determine when and where the payload is released. The goal is to protect heathy tissue by keeping the potent payload contained while circulating in blood, only releasing it once it gets to the target cell or tumor cell.
Some ADCs have prioritized speedy payload release, ensuring the most cancer-killing drug possible gets released but potentially exposing healthy cells in the process. Others have focused on maximizing the stability of the connection to both antibody and payload, increasing the chance to kill cancer cells but also potentially impacting healthy cells that also express the target. There isn’t a one-size-fits-all approach, and depending on the ADC’s target, the optimal level of stability can differ.
What are the different types of ADC targets?
There are many different examples of ADC targets. The ideal targets are overexpressed on cancer cells compared to healthy tissue. The more a target is selectively expressed on a tumor, the more precisely the payload will affect cancerous cells as opposed to healthy cells.
Learn more about our ADC research.
Both ends matter: the linker’s balancing act
Our scientists are researching linker stability with the goal of striking the right balance between attacking the tumor and minimizing damage to healthy cells. Both ends of these bifunctional linkers are important to achieving the desired stability.
- Connection to the antibody: The stability of the linker’s connection to the antibody controls how the payload stays intact while circulating in the body in hopes of reducing harm to healthy cells.
- Connection to the drug: Meanwhile, the linker’s connection to the drug controls the amount of chemotherapy that gets released into the tumor, which powers the ADC to target tumor cells.
“We believe ADCs will be a cornerstone of the future of precision oncology, offering the chance to combine powerful therapies with targeted delivery to treat patients with many common cancer types,” said Alan Northrup, vice president of discovery chemistry, Merck Research Laboratories.
“Our research in bifunctional linkers is focused on finding the right balance to both enable the drug to find its target and also to optimize the timing and release of its payload, ideally killing the tumor in a targeted way that minimizes the damage to healthy cells elsewhere in the body.”
- Alan Northrup
Vice president of discovery chemistry, Merck Research Laboratories
Could linker innovations enable more precision in oncology?
When a linker system is optimized, it can help researchers explore different combinations of antibodies and payloads for different tumor types and patient needs. In that way, linker innovation can enable next-generation ADC designs that are promising for the future of precision medicine in oncology.
By advancing bifunctional linker design, our scientists aim to help drive ADC research and expand what’s possible in cancer care.
Learn more about our work in oncology.
