| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
IGS-1.76 targets the interaction between neuronal calcium sensor 1 (NCS1) and guanine nucleotide exchange factor Ric8a, with a Ki value of 0.7 μM (isothermal titration calorimetry, ITC) and an IC₅₀ value of 1.2 μM (HTRF-based binding inhibition assay) [1]
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| ln Vitro |
The Drosophila NCS-1/IGS-1.76 complex is inhibited by IGS-1.76 [1].
IGS-1.76 (0.1–10 μM) dose-dependently inhibited the interaction between recombinant NCS1 and Ric8a, achieving 52% inhibition at 1 μM and 91% inhibition at 10 μM (HTRF assay) [1] - In primary rat cortical neurons: The compound (1–5 μM) reduced NCS1-Ric8a co-immunoprecipitation by 45–78%, confirming disruption of their endogenous interaction (Western blot) [1] - It modulated calcium-dependent synaptic vesicle exocytosis: 3 μM decreased FM4-64 dye release (a marker of vesicle exocytosis) by 58% in cortical neurons, without affecting baseline calcium levels [1] - IGS-1.76 showed high selectivity for NCS1-Ric8a: no significant binding to other NCS family members (NCS2, NCS3) or GEFs (e.g., GEF-H1) at concentrations up to 20 μM [1] - No obvious cytotoxicity was observed in primary cortical neurons or Neuro-2a cells at concentrations up to 20 μM (MTT assay, cell viability >90%) [1] |
| Enzyme Assay |
ITC assay for NCS1-Ric8a binding affinity: Recombinant human NCS1 protein was dialyzed and mixed with serial dilutions of IGS-1.76 (0.05–10 μM) in buffer at 25°C. Ric8a protein was injected into the sample cell, and heat changes were measured to calculate the binding dissociation constant (Ki) [1]
- HTRF-based binding inhibition assay: NCS1 was labeled with a donor fluorophore, and Ric8a with an acceptor fluorophore. The labeled proteins were incubated with IGS-1.76 (0.1–20 μM) at 37°C for 60 minutes. Fluorescence resonance energy transfer (FRET) signal was detected to assess inhibition of protein-protein interaction [1] |
| Cell Assay |
Primary cortical neuron culture: Cortical neurons were isolated from E18 rat embryos, plated on poly-L-lysine-coated dishes, and cultured in neurobasal medium for 7–10 days before drug treatment [1]
- Co-immunoprecipitation (Co-IP) assay: Neurons were treated with IGS-1.76 (1–5 μM) for 24 hours, lysed, and lysates were incubated with NCS1 antibody. Immunoprecipitated complexes were analyzed by Western blot with Ric8a antibody to detect interaction disruption [1] - Synaptic vesicle exocytosis assay: Neurons were loaded with FM4-64 dye for 10 minutes, washed, and treated with IGS-1.76 (1–5 μM) for 30 minutes. Dye release was induced by high potassium (50 mM KCl), and fluorescence intensity was measured in real-time to quantify exocytosis [1] - Calcium imaging assay: Neurons were loaded with Fluo-4 AM probe, treated with IGS-1.76 (3 μM), and intracellular calcium levels were monitored during KCl stimulation to rule out direct calcium chelation [1] |
| References | |
| Additional Infomation |
IGS-1.76 is a synthetic small molecule inhibitor belonging to the phenothiazine class, designed to target the NCS1-Ric8a protein-protein interaction[1]
- Its mechanism of action involves binding to the hydrophobic pocket of NCS1 (Leu66, Phe72, Ile100 residues), which is crucial for the recognition of Ric8a, thereby blocking the binding between the two[1] - This compound is a valuable tool for studying NCS1-Ric8a-mediated signaling pathways (including the regulation of synaptic function and neuronal excitability)[1] - It is expected to serve as a therapeutic synaptic function modulator for the treatment of neuropsychiatric disorders (such as schizophrenia and epilepsy) associated with abnormal NCS1-Ric8a activity[1] |
| Molecular Formula |
C22H18N2OS
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|---|---|
| Molecular Weight |
358.456123828888
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| Exact Mass |
358.113
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| CAS # |
313480-47-6
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| PubChem CID |
591698
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.700
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| LogP |
5.65
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
441
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GYQWKTIZRYVFEM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H18N2OS/c25-21(24-22-23-19-13-7-8-14-20(19)26-22)15-18(16-9-3-1-4-10-16)17-11-5-2-6-12-17/h1-14,18H,15H2,(H,23,24,25)
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| Chemical Name |
N-(1,3-benzothiazol-2-yl)-3,3-diphenylpropanamide
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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 : ~250 mg/mL (~697.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7897 mL | 13.9486 mL | 27.8971 mL | |
| 5 mM | 0.5579 mL | 2.7897 mL | 5.5794 mL | |
| 10 mM | 0.2790 mL | 1.3949 mL | 2.7897 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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