Rheumatoid arthritis (RA) is a chronic crippling disease of unknown etiol. In recent years different pro-inflammatory cytokines, TNF-α and IL-1β, have been shown to play an important role in the pathogenesis of RA. BLX-1028, an amino acid based small mol., strongly blocked LPS induced TNF-α, IL-6 and IL-1β productions (IC50 0.1-1 μM) whereas, dexamethasone (10 μM) reduced 50% of TNF-α and IL-6 levels compare to control cells. BLX-1028 did not show any cytotoxicity even at 100 μM dose in liver HepG2 cells or other cell types. To characterize further, in a sepsis animal model, BLX-1028 was administered orally to SW mice (50 mg/kg body weight) one hour before LPS challenge and blood was collected after 90 min. BLX-1028 lowered 54% of serum TNF-α and 32% of IL-6 levels compared to vehicle treated animals. When given orally, BLX-1028 significantly improved paw thickness and clin. scores in collagen-induced arthritis in mice within 10 days of treatment. Thus, BLX-1028 may be useful in the treatment of rheumatoid patients who benefit from current TNF-α modulating therapies.