Interferon gene stimulator(STING) is an adaptor protein that can induce the secretion of type I interferon and proinflammatory cytokines. Meanwhile, the protein is activated by bacterial-derived cyclic dinucleotide (CDN) or cytosolic dsDNA (dsDNA). Downstream effects of STING activation include NF-κB. Nonetheless, IRF3 and STAT6 are active. This leads to the production of type I interferon and proinflammatory cytokines, as well as the repolarization of M2 to M1 macrophages.

Besides, STING has a protective effect on inflammation-induced colorectal cancer. In addition, STING deficient mice were less resistant to mutagen-induced inflammation-driven epithelial cancer. Moreover, STING mediates inflammation independently of IRF3. STING can activate ADAM17. And this activation produces soluble proinflammatory SEMA4D independent of the TBK1/IRF3 mediated transcription pathway. Compared with wild-type mice, the severity of septicemia in STING deficient mice was reduced. Furthermore, STING agonist therapy may improve inflammation associated with DSS colitis. Since STING is the medium of the immune system, STING has a feasible therapeutic effect on pathogen infection, cancer, and inflammatory diseases. Today, we will introduce an orally active stimulator of interferon genes (STING) agonist, BSP16.

BSP16 is an Orally Active Stimulator of Interferon Genes (STING).

Above all, BSP16 is a potent, orally active STING agonist. BSP16 can selectively stimulate the STING pathway. BSP16 has potent anti-cancer activity.

Next in importance, BSP16 can selectively stimulate the STING pathway in ISG-THP1 and ISGRAW264.7 cells with EC50 values of 9.24 and 5.71 μM, respectively. Interestingly, BSP16 strongly activates STING signaling in human and mouse cells and binds STING as a homodimer. Particularly, BSP16 exhibits a promising absorption, distribution, metabolism, excretion, and toxicity.

Once again, BSP16 has well tolerated and excellent pharmacokinetic profile. Obviously, BSP16 with 15, 30 mg/kg q3d or 20 mg/kg, q5d by oral induces tumor regression and durable antitumor immunity.

All in all, BSP16 is a potent, orally active STING agonist.


Xi Feng, et al. J Med Chem. 2022 Sep 7.