Discovery of Selenium-Containing STING Agonists as Orally Available Antitumor Agents

Activation of the stimulator of interferon genes (STING)
pathway
to achieve antitumor response is an attractive approach for cancer
immunotherapy. In this study, we report the identification of BSP16 (LF250) as a potent, orally available STING
agonist. BSP16 strongly activates STING signaling in
human and mouse cells and binds STING as a homodimer. A 2.4 Å
cocrystal structure revealed that BSP16 could induce
the “closed” conformation of STING. In vivo studies revealed that BSP16 is well tolerated, has
an excellent pharmacokinetic profile as an oral drug, and induces
tumor regression and durable antitumor immunity. The promising bioactivities
of BSP16 make it valuable for further development as
an antitumor agent.