GIBH-130

GIBH-130 is an effective inhibitor of neuroinflammation. GIBH-130 significantly suppresses the IL-1β secretion by activated microglia (IC₅₀=3.4 nM). IC50 & Target: IC50: 3.4 nM (IL-1β), 46.24 μM (NO), 40.82 μM (TNF-α)^[1] In Vitro: GIBH-130 is a novel antineuroinflammatory 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. The IC₅₀ values of GIBH-130 for NO and TNF-α inhibition are 46.24 and 40.82 μM, respectively. Notably, pretreatment with GIBH-130 significantly suppresses the IL-1β secretion by activated microglia (IC₅₀=3.4 nM). The inhibitory efficiency of GIBH-130 at 20 nM is comparable to 20 μM minocycline against IL-1β release. IL-1β is one of the major cytokines during neuroinflammatory progression of AD. So, it is meaningful to explain the selectivity of GIBH-130 against IL-1β (IC₅₀ value 3.4 nM) over NO and TNF-α (IC₅₀ value 46.24 and 40.82 μM, respectively) ^[1]. In Vivo: GIBH-130 exhibits comparable in vivo efficacy of cognitive impairment relief to donepezil and memantine respectively in both β amyloid-induced and APP/PS1 double transgenic Alzheimer’s murine models at a substantially lower dose (0.25 mg/kg). The pharmacokinetic properties of GIBH-130 are assessed in Sprague-Dawley rats. 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].