| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
S961 TFA targets the insulin receptor, binding with high affinity and selectivity. Its IC50 for the HIR-A isoform is 0.048 nM, and for HIR-B, it is 0.027 nM in a scintillation proximity assay (SPA-assay). It exhibits low affinity for the human insulin-like growth factor I receptor (HIGF-IR), with an IC50 of 630 nM, demonstrating its selectivity for the insulin receptor over the closely related IGF-1R.
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| ln Vitro |
In the PEG-assay, S961 also demonstrates strong affinity for Rat IR and Pig IR, with IC50s of 0.056 nM and 0.084 nM, respectively[1].
S961 TFA is a high-affinity insulin receptor antagonist. In vitro, it binds to the insulin receptor and prevents the binding and downstream signaling of endogenous insulin. The peptide is used in cell culture to block the effects of insulin, allowing researchers to study insulin-independent pathways or to create a model of insulin resistance. By inhibiting insulin receptor activation, it blocks the metabolic (e.g., glucose uptake) and mitogenic (e.g., proliferation) effects of insulin in target cells. |
| ln Vivo |
In vivo, S961 TFA effectively induces hyperglycemia (high blood sugar) in animal models by blocking the action of endogenous insulin. It is administered systemically to create a rapid and reversible model of pharmacological insulin resistance. This is valuable for studying the consequences of insulin deficiency or resistance without the need for genetic manipulations (e.g., knockout models). S961 is used to investigate the effects of insulin blockade on glucose homeostasis, lipid metabolism, and beta-cell function.
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| Enzyme Assay |
A cell-free binding assay for S961 TFA can be performed using surface plasmon resonance (SPR). Recombinant human insulin receptor (HIR) protein is immobilized on a biosensor chip. Increasing concentrations of S961 TFA (0.001-100 nM) are flowed over the chip. Association and dissociation rates are measured, and the equilibrium dissociation constant (KD) is calculated. Alternatively, a scintillation proximity assay (SPA) using [¹2⁵I]-insulin and HIR-containing membranes can be used to determine the IC50 by competition.
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| Cell Assay |
A cell-based insulin receptor activation assay can be performed to measure the antagonist activity of S961 TFA. Cells overexpressing the human insulin receptor (e.g., CHO-IR cells) are seeded in 96-well plates and serum-starved overnight. Cells are pre-incubated with S961 TFA (0.01-1000 nM) for 30 min, followed by stimulation with insulin (1-10 nM) for 10-15 min. Cell lysates are prepared, and the phosphorylation of the insulin receptor (pY1162/1163) or its downstream effector AKT (pS473) is measured by a homogeneous time-resolved fluorescence (HTRF) assay or ELISA. The IC50 for antagonism is the concentration required to inhibit 50% of the insulin-stimulated signal.
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| Animal Protocol |
S961 TFA can be studied in rodent models to induce acute hyperglycemia. Male C57BL/6 mice (8-12 weeks, n=5 per group) are fasted for 4-6 h. Baseline blood glucose levels are measured using a glucometer. S961 TFA (0.1-10 nmol) is administered as a bolus intraperitoneal (i.p.) or subcutaneous (s.c.) injection. Blood glucose levels are then measured at regular intervals (15, 30, 60, 120, 180 min). For chronic studies, S961 is administered via an osmotic minipump (e.g., 10-50 nmol/day) for 7-14 days to induce sustained hyperglycemia. Glucose tolerance tests (GTTs) are performed to assess the degree of insulin resistance.
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| ADME/Pharmacokinetics |
S961 TFA is a peptide with a high molecular weight (approximately 5000 Da) and a complex formula of C211H297N55O71S2. The powder should be stored at -20degC for up to 3 years, sealed and away from moisture. In solvent, it is stable for 1 year at -80degC. The peptide is poorly soluble in water (<1 mg/ml) and should be dissolved in a suitable buffer (e.g., PBS) with sonication. For in vivo use, it is typically formulated in sterile PBS or saline.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for S961 TFA are available. As an insulin receptor antagonist, its pharmacological action is to block insulin signaling. In vivo, this leads to severe hyperglycemia. Therefore, animals treated with S961 require monitoring to prevent prolonged or severe hypoglycemia (contradictorily, it causes hyperglycemia, which can be managed with insulin if necessary). The peptide itself is not cytotoxic, but the induced metabolic state is detrimental. Standard safety precautions for peptide handling should be followed.
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| References | |
| Additional Infomation |
S961 TFA is a research-grade peptide and is not approved for clinical use. It is a powerful tool for inducing insulin resistance in experimental models and is used to study the mechanisms of insulin action, the pathophysiology of diabetes, and the pharmacology of new anti-diabetic drugs. It was first described in a study by Schäffer et al. (2008). This product is for research use only and not for human therapeutic applications.
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| Molecular Formula |
C211H297N55O71S2.C2HF3O2
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|---|---|
| Molecular Weight |
4918.15
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| Related CAS # |
S961 acetate;S961;1083433-49-1
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| Appearance |
White to off-white solid powder
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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 and light. |
| 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) |
H2O :~6.5 mg/mL (~1.32 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2033 mL | 1.0166 mL | 2.0333 mL | |
| 5 mM | 0.0407 mL | 0.2033 mL | 0.4067 mL | |
| 10 mM | 0.0203 mL | 0.1017 mL | 0.2033 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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