BSP16 is a highly potent and orally active STING agonist, capable of selectively stimulating the interferon genes pathway. This compound, BSP16, holds great potential for cancer research [1].

BSP16, at concentrations ranging between 0.1 and 100 μM, selectively activates the STING pathway in both ISG-THP1 and ISGRAW264.7 cells, with half-maximal effective concentration (EC50) values of 9.24 and 5.71 μM, respectively. Additionally, BSP16 (at 10, 25, 50 μM for durations of 1, 3, 6 hours) significantly stimulates STING signaling in human and mouse cells, exhibiting its function by binding to STING as a homodimer. This compound also shows promising ADME (absorption, distribution, metabolism, excretion) and toxicity profiles. Further, RT-PCR and Western Blot analyses conducted on ISG-THP1 cells treated with BSP16 for the specified durations and concentrations robustly induced mRNA expression of IFNβ, CXCL10, and IL6, as well as markedly increased the phosphorylation of TBK1 and IRF3, demonstrating a time and concentration-dependent enhancement of STING activation effects.

BSP16, when administered orally (po, 50 mg/kg) and intravenously (iv, 5 mg/kg), demonstrates excellent tolerability and pharmacokinetic properties. Notably, BSP16, at oral doses of 15 and 30 mg/kg every three days (q3d) and 20 mg/kg every five days (q5d), effectively induces tumor regression and establishes durable antitumor immunity in MC38 and CT26 colon carcinoma syngeneic tumor models. Administration of 15 and 30 mg/kg (oral, q3d) resulted in complete tumor regression after 21 days and a significant increase in IFNB and IL6 at 30 mg/kg. Similarly, a dosage of 20 mg/kg (oral, q5d) achieved tumor regression within 30 days in all treated mice and increased IFNB levels in the plasma of CT26-bearing mice. Pharmacokinetic analysis in rats receiving BSP16 at doses of 5 mg/kg (iv) and 50 mg/kg (po) revealed significant absorption and distribution metrics, illustrating BSP16's potential as an efficacious and well-tolerated therapeutic agent for colon carcinoma.