GIBH-130 markedly inhibits the IL-1β secretion by activated microglia (IC50: 3.4 nM). GIBH-130 is an effective inhibitor of neuroinflammation.

TNF-α:40.82 μM, NO:46.24 μM, IL-1β:3.4 nM

GIBH-130 is a novel anti-neuroinflammatory agent that is identified through microglia-based phenotypic screenings. GIBH-130 (IC50 3.4 nM) is identified in screenings as one of the most effective inhibitors with an acceptable half-life. Pretreatment of microglia with GIBH-130 significantly reduces the production of these factors in response to Lipopolysaccharides (LPS) stimulation, and the extent of the reduction is dependent on the concentrations of GIBH-130. GIBH-130 has weak inhibition for NO (IC50: 46.24 μM) and TNF-α (IC50: 40.82 μM). Notably, pretreatment with GIBH-130 significantly suppresses the IL-1β secretion by activated microglia (IC50: 3.4 nM). The inhibitory efficiency of GIBH-130 (20 nM) is comparable to 20 μM minocycline against IL-1β release. IL-1β is one of the major cytokines during the neuroinflammatory progression of the AD [1].

In both β amyloid-induced and APP/PS1 double transgenic Alzheimer's murine models, GIBH-130 (0.25 mg/kg) has comparable in vivo efficacy of cognitive impairment relief to donepezil and memantine respectively. As a potential drug candidate targeting in CNS, GIBH-130 is found to be orally bioavailable in rats, with 74.91% bioavailability and 4.32 h half-life. In addition, GIBH-130 displays good penetration ability across blood-brain barrier (AUCBrain/Plasma=0.21)[1].