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Purity: ≥98%
| Targets |
GIBH-130's primary mechanism of action is the potent inhibition of IL-1β secretion from activated microglia, a key driver of neuroinflammation. It is identified as a novel antineuroinflammatory agent. While its direct molecular target is not explicitly stated in the search results, its high selectivity for inhibiting IL-1β (IC50 = 3.4 nM) over other inflammatory mediators like NO (IC50 = 46.24 μM) and TNF-α (IC50 = 40.82 μM) suggests a specific mechanism of action.
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| ln Vitro |
GIBH-130 is a brand-new anti-inflammatory medication that was found using a phenotypic screen based on microglia. The screen revealed GIBH-130 (IC50 3.4 nM) as one of the most effective inhibitors with a reasonable half-life. The production of these lipopolysaccharide (LPS)-stimulated components was greatly reduced in microglia pretreated with GIBH-130; the extent of the reduction was dependent on the concentration of GIBH-130. GIBH-130's inhibitory concentrations against NO and TNF-α were 46.24 and 40.82 μM, respectively. Notably, activated microglia's release of IL-1β was markedly suppressed by GIBH-130 pretreatment (IC50=3.4 nM). 20 μM minocycline and 20 nM GIBH-130 both had similar inhibitory effects on the release of IL-1β. One of the primary cytokines in the development of AD neuroinflammation is IL-1β. Thus, it seems sense to discuss how GIBH-130 is more selective for IL-1β (IC50 value 3.4 nM) than for NO and TNF-α (IC50 values 46.24 and 40.82 μM, respectively) [1].
In vitro, GIBH-130 is a highly potent inhibitor of neuroinflammation. It significantly suppresses IL-1β secretion by activated microglia with an IC50 of 3.4 nM. Its inhibitory efficiency at 20 nM is comparable to that of 20 μM minocycline, a well-known anti-inflammatory agent. The compound also inhibits the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α), but with much higher IC50 values (46.24 μM and 40.82 μM, respectively), indicating its strong selectivity for IL-1β. |
| ln Vivo |
In mouse models of Alzheimer's disease caused by amyloid-β toxicity and APP/PS1 double-transgenic mice, GIBH-130 showed similar in vivo cognitive performance to donepezil and memantine, but at substantially lower doses (0.25 mg/kg), respectively. effects of removing obstacles. GIBH-130's pharmacokinetic characteristics were assessed in Sprague-Dawley rats. GIBH-130 is a prospective CNS-targeting drug candidate having an oral bioavailability of 74.91% and a half-life of 4.32 hours in rats. Furthermore, GIBH-130 exhibits good ability to penetrate the blood-brain barrier (AUCBrain/Plasma=0.21) [1].
In vivo, GIBH-130 has demonstrated significant efficacy in rodent models of Alzheimer's disease. In both β-amyloid-induced and APP/PS1 double transgenic mouse models, it exhibited cognitive impairment relief comparable to donepezil and memantine at a substantially lower dose of 0.25 mg/kg. It has also shown promise in reducing neurodegeneration and motor deficits in a hemiparkinsonian model. |
| Enzyme Assay |
In vitro enzymatic or receptor binding assays for GIBH-130 are not detailed in the search results. Its activity is primarily characterized through cell-based phenotypic screenings that measure the inhibition of IL-1β secretion from activated microglia.
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| Cell Assay |
In vitro cell-based assays for GIBH-130 involve treating activated microglia with the compound and measuring the production of pro-inflammatory cytokines. Specifically, microglia are stimulated with Lipopolysaccharides (LPS), and the inhibitory effect of GIBH-130 on the secretion of IL-1β, TNF-α, and NO is quantified. The IC50 values for these different endpoints are then determined.
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| Animal Protocol |
In vivo animal experiments for GIBH-130 have been conducted in several disease models. In Alzheimer's disease models, including β-amyloid-induced and APP/PS1 double transgenic mice, the compound is administered at a low dose of 0.25 mg/kg to assess its effect on cognitive function. It has also been evaluated in a hemiparkinsonian model for its effects on neurodegeneration and motor deficits.
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| ADME/Pharmacokinetics |
GIBH-130 displays favorable pharmacokinetic properties for a CNS-targeting drug. In Sprague-Dawley rats, it demonstrates high oral bioavailability of approximately 74.91% and a half-life of about 4.32 hours. It also shows moderate blood-brain barrier penetration, with a brain-to-plasma AUC ratio of approximately 0.21.
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| Toxicity/Toxicokinetics |
Available safety data indicates that GIBH-130 is a hazardous substance. It is described as very toxic if swallowed (R28), irritating to skin (R38), and carrying a risk of serious damage to eyes (R41). It may also decompose and emit toxic fumes under fire conditions. Appropriate safety measures should be taken when handling this compound.
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| References | |
| Additional Infomation |
GIBH-130 is a novel and potent inhibitor of neuroinflammation, distinguished by its high selectivity for suppressing IL-1β secretion from activated microglia. Its remarkable in vivo efficacy in Alzheimer's disease models at a very low dose highlights its potential as a therapeutic candidate for neurodegenerative diseases. The compound is also known as AD-16.
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| Molecular Formula |
C20H20N6O
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|---|---|
| Molecular Weight |
360.412403106689
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| Exact Mass |
360.169
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| CAS # |
1252608-59-5
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| Related CAS # |
1252608-59-5
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| PubChem CID |
50938773
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| Appearance |
Off-white to pink solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
483
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1=NN=C(C2=CC=CC=C2)C=C1C)(N1CCN(C2=NC=CC=N2)CC1)=O
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| InChi Key |
ZTJHTEHADIHZJS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H20N6O/c1-15-14-17(16-6-3-2-4-7-16)23-24-18(15)19(27)25-10-12-26(13-11-25)20-21-8-5-9-22-20/h2-9,14H,10-13H2,1H3
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| Chemical Name |
(4-methyl-6-phenylpyridazin-3-yl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone
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| Synonyms |
GIBH-130 GIBH 130 GIBH130.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~138.73 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7746 mL | 13.8731 mL | 27.7462 mL | |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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