Preclinical characterization of novel multi-client inhibitors of Sec61 with broad antitumor activity

We are proud of our contribution to the discovery of small molecule inhibitors of Sec61, a novel anti-cancer therapeutic target.

While Sec61 has long shown therapeutic potential for blocking the expression of pro-tumorigenic factors, earlier drug candidates were limited by poor tolerability and suboptimal pharmaceutical properties, which hindered their clinical development.

In the recent study, “Pre-clinical characterization of novel multi-client inhibitors of Sec61 with broad anti-tumor activity,” we collaborated with Kezar Life Sciences, the University of Helsinki, UCB, and University of California, San Francisco to advance our understanding of the Sec61 inhibitor KZR-261. Our team used cryo-EM to solve the structure of KZR-261-bound Sec61, providing critical insights into its mechanism of action and how it compares to other inhibitors.

KZR-261 has now advanced to Phase I clinical trials, where it has shown promising tolerability and early signs of disease stabilization, underscoring the potential of Sec61 inhibition as a novel anticancer strategy.