GIBH-130

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种新型神经炎症抑制剂，可抑制 LPS 刺激的 N9 小胶质细胞中促炎细胞因子的产生 (IC50=3.4 nM)。

A novel inhibitor of neuroinflammation, suppresses the proinflammatory cytokine production in LPS-stimulated N9 microglial cells (IC50=3.4 nM); modulates the release of detrimental proinflammatory cytokines; exhibits in vivo efficacy of cognitive impairment in both β amyloid-induced and APP/PS1 double transgenic Alzheimer's murine models.Alzheimer's Disease Phase 1 Clinical.

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) .

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).

GIBH 130 | GIBH130

Others

Other Targets

IL-1β

Neurological Disease

Alzheimer Disease

1252608-59-5

360.421

C20H20N6O

>98% (HPLC)

< 1 mg/ml refers to the product slightly soluble or insoluble

O=C(C1=NN=C(C2=CC=CC=C2)C=C1C)N3CCN(C4=NC=CC=N4)CC3

(4-methyl-6-phenylpyridazin-3-yl)(4-(pyrimidin-2-yl)piperazin-1-yl)methanone

(-20℃)

With Ice Pack

≥ 2 years