Anti‐inflammatory property of BLX‐1060, an orally active TNF‐α inhibitor

Abstract

BLX-1060 is a water-soluble orally active, modified amino acid derived molecule with no structural resemblance with any existing anti-inflammatory compounds. Designed and synthesized by using a technology platform of combining “smart chemistry” and “rational drug design approach” (RDDA). In a sepsis model, when BLX-1060 was given orally to SW mice at three different doses 25, 50 and 100 mg/kg body weight before one hour LPS challenge, it significantly lowered TNF-α levels by 20, 46 and 69 percent, respectively compared to vehicle treatment animals. IL-6 levels were also lowered after treatment with BLX-1060. Similarly, when collagen induced arthritis mice were treated with BLX-1060 in two different sets of experiment, 25 and 50 mg/kg doses for 21 days, it significantly lowers clinical score and paw thickness by more than 40 percent in 50 mg/kg dose, whereas no significant difference was observed in 25 mg/kg dose. Body weight and food intake were increase with no significant difference in both the dose group. The levels of serum TNF-α measured at the end of study revealed that BLX-1060 at 50 mg/kg body weight dose lowered TNF- α levels significantly by 45 percent, whereas, at 25 mg/kg dose no significant difference was observed. In Adjuvant induced arthritis rats BLX-1060 at 50 mg/kg/day, PO significantly reduced clinical symptoms of arthritis (32%) and paws volume (12%). X-rays of the paws upon termination showed an improvement in bone density compare to vehicle. These combined results demonstrate the potential of BLX-1060 as a novel therapeutic lead for all indications where TNF- α play a major role.