Anti-inflammatory and Anti-arthritic Effects of a Novel XXXX Analogue, UTL-5b (GBL-5b).

@entity32 @entity137 @entity6963 @entity625 @entity326 @entity19 @entity4 @entity8688 @entity35 @entity204 @entity637 @entity309
@entity309 ( @entity309 ) is a common disease characterized by @entity32 and irreversible destruction of articular cartilage and bone. In this report, we examined the anti-inflammatory and anti-arthritic effects of a novel @entity6963 analogue, UTL-5b (also known as GBL-5b), for potential @entity309 treatment. Using a carrageenan-induced @entity4 study in @entity35 , UTL-5b exhibited a better anti-inflammatory effect as compared with @entity6963 and its metabolite. The chronic efficacy of UTL-5b was examined using type II collagen-induced @entity625 (CIA) @entity19 model. UTL-5b exerted an anti-arthritic effect in a dose-dependant manner with @entity19 given 30 mg/kg exhibiting amelioration of disease early in the trial, but losing statistical significance over time. In contrast, @entity19 treated with 60 mg/kg showed reduced clinical disease parameters early in the trial and these effects were sustained over the ten week trial period. Mechanistic studies indicate that UTL-5b is an inhibitor of @entity637 production in vivo. Oral administration of UTL-5b prior to i.p. injection with lethal dose of lipopolysaccharide (LPS)/ @entity8688 markedly reduced the levels of serum @entity637 and increased survival rates of animals from @entity326 -induced @entity204 . Acute @entity137 study using @entity19 receiving increasing doses of UTL-5b showed that no animals were killed by UTL-5b at 2,000 mg/kg (LD(50) >2,000 mg/kg). Our studies show that UTL-5b represents a novel anti-inflammatory and anti-arthritic agent with potential therapeutic application for @entity309 treatment.
