Sygnature Discovery contributes to newly approved therapy Lifyorli™

Sygnature Discovery is pleased to mark an important milestone in a long-running collaboration with Corcept Therapeutics, following the recent approval of Lifyorli™, a treatment developed and advanced by Corcept Therapeutics.

Sygnature supported the early discovery and optimization of relacorilant, one of the components of this therapy, through an integrated drug discovery collaboration that began more than a decade ago. Scientists from Sygnature were named as inventors on the associated patent and are co-authors on the Journal of Medicinal Chemistry publication describing the discovery of the molecule.

“Seeing a molecule we helped co-design and synthesize progress from concept to approval is incredibly rewarding,” said Dr Benoit Gourdet, a lead scientist on the program from Sygnature Discovery. “It reflects our approach of designing with the full discovery journey in mind, not just the next milestone, and shows what can be achieved through integrated, cross-disciplinary teams working in close collaboration with our clients. We congratulate everyone involved in reaching this milestone.”

A long-term, integrated discovery collaboration

The collaboration between Sygnature Discovery and Corcept brought together medicinal chemistry, computational design, biology, DMPK, and in vivo expertise to address the challenges of designing selective glucocorticoid receptor antagonists. Working as an integrated extension of Corcept’s discovery team, Sygnature scientists contributed to the iterative design, synthesis, and optimization of compounds during the early phases of the program.

This work is described in detail in a Journal of Medicinal Chemistry paper published in 2017, which outlines the discovery and optimization of relacorilant and the scientific rationale behind key design decisions. The publication provides a transparent account of the medicinal chemistry strategy underpinning the program and remains part of the public scientific record.

A case study describing the collaboration and Sygnature’s role in the discovery phase is available here. This captures how the teams worked together day to day to progress the program.

Continuing the science: new medicinal chemistry publication

Alongside the approval milestone, a new Journal of Medicinal Chemistry paper has now been published, building on the scientific foundations of the original relacorilant program.

The new work explores a structurally simplified series inspired by relacorilant, with the aim of understanding how changes to the molecular architecture influenced biological activity. As part of this research, three compounds from the simplified series were progressed into in vivo models, where they demonstrated activity.

This follow-on study reflects a continued focus on learning from existing chemical matter and using those insights to inform future design strategies. It also highlights the value of revisiting established programs to ask new scientific questions and test alternative hypotheses.

Designing for the full discovery journey

Across both publications, the work reflects Sygnature Discovery’s approach to drug discovery: combining integrated disciplines with early consideration of how compounds may need to perform later in development. Rather than focusing solely on the next step in the discovery process, the teams aimed to design molecules with the broader discovery and development pathway in mind.

While Corcept led the clinical development and approval of Lifyorli™, Sygnature is proud to have contributed to the early scientific foundations that helped enable the program to progress.

The approval of Lifyorli™, alongside the publication of new medicinal chemistry research, underscores the long timelines involved in drug discovery and the importance of collaborative, well-integrated teams in navigating them successfully.