Paul Scherrer Institute Advances Light Controlled Drug Development with Breakthrough in Photopharmacology Research

Jörg Standfuss (left) and Quentin Bertrand are two of the researchers in the PSI Center for Life Sciences who now have found out, on the molecular level, why a light-controllable drug changes its potency. © Paul Scherrer Institute PSI/Markus Fischer

(IN BRIEF) Researchers at the Paul Scherrer Institute have identified the molecular mechanism behind a light-switchable drug that can modulate its effectiveness in treating high blood pressure. By observing how the compound changes shape and interacts with its receptor, the team demonstrated how light can be used to fine-tune drug activity rather than simply turning it on or off. The study, conducted using advanced imaging at the SwissFEL facility, provides a foundation for developing more precise, targeted therapies with reduced side effects. The findings mark an important step forward in photopharmacology and open new possibilities for controlling drug activity in real time within the body.

(PRESS RELEASE) VILLIGEN, 19-Mar-2026 — /EuropaWire/ — The Paul Scherrer Institute (PSI) has advanced research into light-controlled medicines by uncovering how a photoswitchable drug for high blood pressure changes its effectiveness at the molecular level. The findings, published in Angewandte Chemie International Edition, provide new insights that could support the development of drugs whose activity can be precisely regulated inside the body using light.

The research focuses on photopharmacology, an emerging field that aims to create medicines that can be activated or deactivated using specific wavelengths of light. Such an approach could allow treatments to be targeted to specific areas of the body, minimizing side effects by ensuring that drugs remain inactive elsewhere. For example, a cardiovascular drug could be activated only in heart tissue while leaving other organs unaffected.

Scientists at the PSI Center for Life Sciences investigated how a light-responsive beta blocker interacts with its biological receptor. The compound, known as photoazolol-1, is based on a well-established class of drugs used to treat high blood pressure and heart rhythm disorders. It binds to β-adrenergic receptors, which play a key role in regulating heart rate and blood pressure in response to stress hormones such as adrenaline.

The unique feature of photoazolol-1 lies in its ability to change shape when exposed to light. Developed in collaboration with researchers from the Consejo Superior de Investigaciones Científicas in Barcelona, the molecule includes an azobenzene component that rapidly switches configuration when irradiated with violet light. This transformation occurs within picoseconds, causing the molecule to bend and increase in size.

PSI researchers discovered that the molecule’s straight form fits precisely into the receptor’s binding site, allowing it to effectively block receptor activity. When the molecule switches to its bent configuration, it remains in the binding pocket but binds less strongly, reducing its ability to inhibit the receptor. Rather than simply turning the receptor “on” or “off,” the light-triggered change allows for a more nuanced modulation of its activity.

Importantly, the bent form of the molecule is less stable and gradually reverts to its original shape over time, although exposure to green light can accelerate this process. This dynamic behavior allows researchers to control the drug’s activity with a high degree of precision.

Earlier experiments conducted by collaborating teams demonstrated the practical effects of this mechanism in living cells. Heart cells exposed to the light-switchable compound could have their beating rate adjusted by varying light exposure. The PSI study now provides a detailed atomic-level explanation for these observed effects.

The research was carried out using the SwissFEL X-ray free-electron laser facility, which enables scientists to capture ultrafast molecular changes in real time. By generating extremely short and intense light pulses, SwissFEL allows researchers to observe molecular transformations as if creating a frame-by-frame film.

The study also involved leadXPro, a PSI spin-off focused on drug discovery through detailed analysis of membrane proteins. The findings offer a more precise understanding of how light-switchable drugs behave, reducing reliance on trial-and-error approaches in molecular design and opening new possibilities for targeted therapies.

Looking ahead, the research team plans to extend this approach to other biological systems, including receptors involved in immune responses and neurological processes. Potential applications include light-activated compounds targeting histamine or adenosine receptors, which are relevant to conditions such as autoimmune diseases and Parkinson’s disease.

Supported by the Swiss National Science Foundation, the work represents a significant step toward making light-controlled therapies a practical reality, with the potential to improve treatment precision and reduce unwanted side effects in a wide range of medical applications.

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SOURCE: Paul Scherrer Institute