New method of drug discovery and development offers better understanding of how drugs work

According to a new study published in Nature Communications, researchers at the Department of Laboratory Medicine, Karolinska Institutet, have made a significant leap in drug discovery and development with a new method called CeTEAM. This approach connects how drugs bind to their targets inside cells with the effects they produce, offering a clearer understanding of how a drug works.

According to the researchers, CeTEAM could become a vital tool that could transform how new therapies are developed and evaluated, ultimately improving treatments for patients.

“CeTEAM allows us to see how drugs interact with their targets in live cells, which is crucial for understanding their effects,” says Nicholas Valerie, Assistant Professor at the Department of Laboratory Medicine and the study’s lead author.

“This method demonstrates that variants of known therapeutic targets, such as the DNA repair protein PARP1, can be useful for understanding how potential drugs act, including intended effects and unintended side effects. For instance, when some drugs bind to PARP1, they can sometimes trap it on DNA, thereby affecting its function and the therapeutic response in patients.”

More efficient screening of drugs in cells and preclinical models

Traditional methods have struggled to link target binding (also called drug-target engagement) to cellular responses of a given drug. Valerie explains, “Our new method provides insights that might otherwise be difficult to obtain, helping us identify which drugs might be most beneficial for patients. The study also reveals that protein variants that can be used to visualize drug interactions may be more common than previously thought, expanding the potential applications of CeTEAM.”

One of the key advantages of CeTEAM is its ability to measure a drug interacting with its protein target without changing the cellular environment. This means researchers can observe how cells respond to drugs over time and gain insights into their mechanism-of-action.

Mikael Altun, Associate Professor at the Department of Laboratory Medicine and a senior author of the study, states, “Because of how our approach works, we can screen many drugs at once, making the process faster and more efficient. The method is also useful for visualizing target engagement in preclinical models, providing a better understanding of how drugs work in complex biological systems.”

The research team is excited about the possibilities that the CeTEAM method offers. Future steps include understanding why certain protein variants work better for the method, expanding its use to different types of drugs, and exploring drug target selectivity in cells. Valerie emphasizes, “This method could lead to more efficient discovery of new drugs that benefit patients across various diseases.”