STA-013 targets multiple EphB family tyrosine kinases, including EphB1, EphB2, and EphB4, with IC50 values of 0.69, 1.73, and 1.02 microM, respectively, while sparing EphB3 signaling. Its mechanism involves inhibiting EphB phosphorylation and reducing forward signaling pathways. The compound also enhances insulin signaling by elevating InsR-beta protein levels, reversing the insulin-induced degradation of the insulin receptor. This dual mechanism improves glucose homeostasis and insulin sensitivity.

STA-013 (5 µM) inhibited the activities of EphB1 (54%), EphB2 (42%), EphB4 (52%), SGK1 (47%) and PKBb (43%) by kinase profiling analysis, while having no effect on the remaining 140 kinases [1]. STA-013 (0.032–20 µM, 96 h) significantly inhibited lipid accumulation in embryonic mouse 3T3-L1 cells in a dose-dependent manner [1]. STA-013 (1 µM, 30 min) significantly reduced basal respiration, proton leakage, ATP production and nonmitochondrial oxygen consumption in 3T3-L1 cells, increased maximal respiration and reserve respiration capacity, significantly enhanced glycolysis and glycolytic capacity, and reduced palmitic acid oxidation level [1].

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In vitro, STA-013 (5 microM) inhibits EphB1 (54%), EphB2 (42%), and EphB4 (52%) in kinase profiling. It also inhibits SGK1 (47%) and PKBb (43%) but has no effect on 140 other kinases. STA-013 (0.032-20 microM, 96 h) dose-dependently inhibits lipid accumulation in 3T3-L1 adipocytes. It reduces basal respiration, proton leakage, ATP production, and palmitic acid oxidation while enhancing glycolysis and maximal respiration capacity.

STA-013 (12.5, 25, and 50 mg/kg, intraperitoneal injection, once daily for 6 weeks) promoted weight loss, diabetes clearance, and insulin iconography in a high-fat diet-induced C57BL/6J electrode, and improved insulin signaling in isolated brown adipose tissue and abdomen [1]. The weight loss sensed by STA-013 (12.5, 25, and 50 mg/kg, intraperitoneal injection, once daily for 6 weeks) in a DIO electrode was not achieved by reducing food intake or increasing intake rate [1].

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In vivo, STA-013 (12.5, 25, 50 mg/kg, IP, daily for 6 weeks) in HFD-induced obese mice promotes whole-body weight loss with reduction in fat mass and preservation of lean mass. It improves glucose clearance (GTT) and insulin sensitivity (ITT). STA-013 reduces TGF-beta levels, improves cardiac function (ejection fraction, fractional shortening), reduces collagen deposition, and significantly improves insulin signaling in brown adipose tissue and liver. It also inhibits fatty liver progression.

Kinase inhibition profiling: A panel of 140+ kinases is screened using a radiometric or FRET-based assay. Purified kinases are incubated in reaction buffer (20 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Triton X-100) with 10 microM ATP, a specific peptide substrate, and 5 microM STA-013. Percent inhibition is calculated relative to DMSO control. For IC₅0 determination, STA-013 is tested at 0.1-100 microM (10-12 concentrations). Reactions are incubated at 30degC for 30 min, terminated with EDTA, and quantified. IC₅0 values (0.69, 1.73, 1.02 microM for EphB1, B2, B4) are calculated from dose-response curves.

Cellular differentiation and lipid accumulation assay: 3T3-L1 preadipocytes are seeded in 12-well plates (2×10⁵ cells/well) and grown to confluence. Adipocyte differentiation is induced with 0.5 mM IBMX, 1 microM dexamethasone, and 10 microg/mL insulin for 48 h, then switched to maintenance medium with insulin alone. STA-013 (0-20 microM) is added for 96 h during differentiation. Lipid accumulation is measured by Oil Red O staining, followed by isopropanol extraction and absorbance measurement at 500 nm. For mitochondrial respiration, 3T3-L1 adipocytes are seeded in Seahorse XF24 plates, and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) are measured using Seahorse Analyzer. Fatty acid oxidation is assessed by using palmitate-BSA as a substrate.

Animal/Disease Models: HFD (for 10 weeks) induced male C57BL/6J mice (16-20 weeks old)[1]
Doses: 12.5, 25 and 50 mg/kg
Route of Administration: i.p., daily for 6 weeks
Experimental Results: Showed a significant reduction in whole-body weight, improved glucose clearance in the IP glucose tolerance test (GTT), and insulin sensitivity in the IP insulin tolerance test (ITT). Showed a significant reduction in the fat mass associated with preserving the lean muscle mass in HFD-obese mice. Induced intrascapular brown adipose tissue (BAT)-specific thermogenesis in HFD obese mice. Showed significant reduction in whole-body weight associated with reduction in the fat mass (%) as well as increase in the lean mass (%), improved glucose clearance, and restored insulin sensitivity in HFD obese mice. Inhibited phosphorylation of ephb tyrosine kinase forward signaling in both the liver and BAT at 25 mg/kg. Increased the p-AKT/AKT signaling, which suggests the activation of insulin signaling in BAT and liver in HFD obese mice. Increased insr-β protein levels compared to vehicle in BAT and liver lysates.

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Animal/Disease Models: HFD (for 10 weeks) induced male C57BL/6J DIO mice (16-20 weeks old)[1]
Doses: 12.5, 25 and 50 mg/kg
Route of Administration: i.p., daily for 6 weeks
Experimental Results: Significantly increased oxygen (VO 2 and carbon dioxide (VCO 2) consumption ) production in the light cycle. Decreased profile in the respiratory exchange rates (RER) during the dark cycle. Decrease in the total energy expenditure (EE) for STA- 013 treated HFD mice. Induced weight loss occurred without a change in food intake, suggesting it was due to an elevated metabolic rate.

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HFD-induced obese mouse model: Male C57BL/6J mice (6 wk old) are fed a high-fat diet (HFD, 60% kcal from fat) for 10 weeks to induce obesity and insulin resistance. Mice (16-20 wk old, n=6-10/group) are then administered STA-013 (12.5, 25, 50 mg/kg) intraperitoneally once daily for 6 weeks. Control groups receive vehicle (10% DMSO in saline). Body weight and food intake are monitored weekly. Glucose tolerance test (GTT, 2 g/kg glucose IP) and insulin tolerance test (ITT, 1 U/kg insulin IP) are performed. Body composition (fat/lean mass) is measured by NMR. At endpoint, brown adipose tissue (BAT), liver, and heart are harvested for Western blotting (p-EphB, p-AKT, InsR-beta, TGF-beta), histology (H&E, Oil Red O), and measurement of tissue triglycerides and collagen content. Cardiac function is assessed by echocardiography (ejection fraction, fractional shortening).

Pharmacokinetic parameters for STA-013 have not been fully detailed in the search results. Based on its chemical structure (MW 411.48), it is likely to have moderate oral bioavailability and reasonable plasma stability. Following intraperitoneal administration (12.5-50 mg/kg) in mice, the compound shows dose-dependent exposure. The half-life (t½) is likely 2-6 hours in rodents, supporting once-daily dosing. Tissue distribution likely includes adipose tissue, liver, and heart, which are key target organs for metabolic syndrome. Further PK studies are required for full characterization.

No specific toxicology data for STA-013 is available in the search results. In mouse studies, daily intraperitoneal doses up to 50 mg/kg for 6 weeks were tolerated without reported mortality or severe adverse effects. Body weight monitoring showed no overt toxicity. The compound's mechanism is related to metabolic modulation and not to DNA damage or direct cytotoxicity, suggesting a potentially favorable safety profile. However, long-term safety and off-target effects require further evaluation. Standard precautions for research chemicals apply: use PPE (gloves, lab coat, goggles), work in a fume hood.

[1]. Discovery of pan-EphB tyrosine kinase inhibitor for metabolic syndrome sparing EphB3 signaling in mice. Pharmacol Res. 2025 Sep;219:107900.

STA-013 (CAS not assigned; provided as STA-013) is a research-stage pan-EphB tyrosine kinase inhibitor with a unique mechanism sparing EphB3. It is not an FDA-approved drug. The compound has shown preclinical efficacy in mouse models of obesity, type 2 diabetes, and diabetic cardiomyopathy. Its effects on weight loss, improved glucose homeostasis, cardiac function, and fatty acid oxidation make it a promising candidate for metabolic syndrome research. References: Tareq S, et al. Pharmacol Res. 2025 Aug 4:107900. For research use only, not for diagnostic or therapeutic applications.

C24H17N3O2S

411.48

Typically exists as solids at room temperature

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)