| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Insulin-like Growth Factor Binding Proteins (IGFBPs). Specifically, NBI-31772 targets the IGF-I/IGFBP-3 complex. By binding to IGFBPs with high affinity, it prevents them from sequestering IGF-I, leading to an increase in the concentration of free, bioavailable IGF-I (Kᵢ = 1-24 nM for all six human subtypes).
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| ln Vitro |
In vitro, NBI-31772 effectively displaces IGF-I from human IGFBP-3 in a dose-dependent manner, as measured by a radioimmunoassay or ELISA. It shows no significant affinity for the IGF-I receptor itself, making its mechanism strictly through IGFBP inhibition. It exhibits potent binding affinities (Kᵢ) ranging from 1 to 24 nM across the six human IGFBP subtypes.
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| ln Vivo |
At the time of ischemia initiation, NBI-317772 (5-100 μg; icv; immediately or at 1, 2, or 3 hours after MCAO) also reduced infarct size in a dose-dependent manner. The highest dose (100 μg) considerably reduced the volume of the infarct, both total and cortical[3].
NBI-31772 has demonstrated significant in vivo activity in rodent models. When administered intracerebroventricularly (icv) to rats, it produces anxiolytic- and antidepressant-like effects, which are mediated by the increased release of bioactive IGF-I in the brain. It also shows neuroprotective effects in models of ischemic brain injury, reducing infarct volume after middle cerebral artery occlusion (MCAO). |
| Enzyme Assay |
A non-cellular binding assay for NBI-31772 is performed to measure its affinity for IGFBPs. This is typically done using a competitive displacement assay. A fixed concentration of a radiolabeled ligand (e.g., ¹2⁵I-IGF-I) is incubated with a purified human recombinant IGFBP protein. Various concentrations of NBI-31772 are added to compete with the labeled IGF-I. After incubation, the bound and free ligands are separated (e.g., by charcoal or by filtration), and the radioactivity in the bound fraction is counted to calculate the Kᵢ or IC50.
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| Cell Assay |
In vitro cellular assays to confirm IGFBP inhibition are not standard, as IGFBPs are secreted proteins. Instead, cell-free displacement assays are used. However, to demonstrate the functional effect of increased free IGF-I, a cellular assay can be performed using cells expressing the IGF-I receptor (e.g., MCF-7 breast cancer cells). Cells are treated with a fixed concentration of the IGF-I/IGFBP-3 complex in the presence of increasing concentrations of NBI-31772. The release of bioactive IGF-I is then measured by quantifying the phosphorylation of the IGF-I receptor (p-IGF-IR) or its downstream signaling effectors like Akt via Western blotting.
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| Animal Protocol |
Animal/Disease Models: SD (Sprague-Dawley) rats (subtemporal middle cerebral artery occlusion model, MCAO)[3]
Doses: 5-100 μg Route of Administration: Icv; immediately or at 1, 2, or, 3 hrs (hours) after MCAO Experimental Results: Resulted in a significant reduction of the total and cortical lesion volume. In vivo animal studies for neuroprotection are conducted using the transient middle cerebral artery occlusion (tMCAO) model in Sprague-Dawley rats. NBI-31772 is administered via intracerebroventricular (icv) injection at doses ranging from 5 to 100 ug, either immediately or up to 3 hours after the induction of ischemia. After 24 hours of reperfusion, the animals are sacrificed, and their brains are sectioned and stained (e.g., with TTC) to measure the infarct (lesion) volume. A reduction in infarct size compared to vehicle-treated controls indicates neuroprotective efficacy. |
| ADME/Pharmacokinetics |
Standard pharmacokinetic data (e.g., half-life, clearance, oral bioavailability) for NBI-31772 are not widely available in public databases. Its in vivo effects are observed following direct central (icv) administration, suggesting it may have poor blood-brain barrier penetration or rapid peripheral clearance when given systemically, limiting its utility as a systemic drug.
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| Toxicity/Toxicokinetics |
Detailed preclinical toxicity profiles (e.g., LD50, NOAEL) for NBI-31772 are not available in standard public databases. As a compound that elevates free IGF-I levels, chronic administration could theoretically be associated with mitogenic and proliferative risks, including the potential for promoting tumor growth. Safety data would be required for therapeutic development.
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| References |
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| Additional Infomation |
NBI-31772 has primarily been investigated as a research tool to study the biological roles of IGFBPs in the central nervous system. Its ability to increase free IGF-I in the brain has shown proof-of-concept for treating conditions like anxiety, depression, and stroke. However, to date, it has not been approved for clinical use.
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| Molecular Formula |
C17H11NO7.7/4H2O
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|---|---|
| Molecular Weight |
372.82
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| Related CAS # |
NBI-31772;374620-70-9
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| Appearance |
Light brown to yellow solid powder
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| SMILES |
O=C(C1=CC(O)=C(O)C=C1)C2=NC(C(O)=O)=CC3=C2C=C(O)C(O)=C3.O
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: ~100 mg/mL (~268.2 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (6.71 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6823 mL | 13.4113 mL | 26.8226 mL | |
| 5 mM | 0.5365 mL | 2.6823 mL | 5.3645 mL | |
| 10 mM | 0.2682 mL | 1.3411 mL | 2.6823 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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