Article type:
Research
Estimated read time:
2 mins min read
Published:
14/10/2025
Scientists found two new drug candidates, UM-242 and UM-259, that can turn down an overactive part of the immune system called STING. Too much STING activity causes harmful inflammation in diseases like lupus. These compounds worked well in lab tests on both human and mouse cells. They aren’t yet suitable as pills, but with further improvements, they could lead to new treatments for autoimmune diseases.
Why it Matters Aberrant STING activation is a key driver of several autoimmune and autoinflammatory conditions. The discovery of UM-242 and UM-259 provides new chemical scaffolds for potential therapies. Unlike some earlier inhibitors, these compounds show potency across different human STING variants and in primary immune cells, making them more clinically relevant.
Hope for the Future Future research will focus on modifying these compounds to improve oral bioavailability and pharmacokinetics while maintaining potency. This could pave the way for safe and effective STING inhibitors to treat diseases such as SLE, AGS, and SAVI.
Read more
Background The cGAS–STING pathway is crucial for detecting foreign DNA and triggering immune defences. While vital for fighting infections, its overactivation is linked to diseases such as amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and STING-associated vasculopathy with onset in infancy (SAVI). This has made STING a major target for drug development. Previous compounds like BB-Cl-amidine and LB244 showed promise but had issues with selectivity and oral bioavailability.
What the Study Found The researchers developed two new compounds, UM-242 and UM-259, built on a novel nitrofuran amidine scaffold.
- Both effectively blocked STING signalling in mouse and human cells, including primary CD14+ monocytes.
- They worked against the most common human STING allele (R232) and suppressed inflammatory cytokines like IFNβ and IL6.
- Mechanistically, they prevented STING oligomerization, like LB244.
- However, they showed limited oral bioavailability, likely due to their thiol-reactive warheads.
Citation Barasa et al., ACS Omega 2025, 10, 41693−41706
Authors Leonard Barasa, Leo DeOrsey, Maeve D. O’Reilly, Shruti Choudhary, Sara E. Cahill, Anukriti Mathur, Sakshi Rajoria, Robert Madison Green, Akumalla Allabaji, Shreekrishna Nellikkalaya, Sourav Paul, Srinivasa Rao Vidadala, Sujit Kumar Sarkar, Santoshkumar N. Patil, Jeffrey Hale, Fiachra Humphries, Katherine A. Fitzgerald, Paul R. Thompson
Date of publication 4/9/25