| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SBI-993 targets the transcription factor MondoA (also known as MondoA) and its binding partner Mlx. MondoA is a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that forms a heterodimer with Mlx. This complex localizes to the nucleus in response to glucose levels and regulates the expression of genes involved in glucose metabolism, lipid synthesis (including thioredoxin-interacting protein, TXNIP), and cellular stress responses. MondoA is a negative regulator of insulin signaling: its activation reduces insulin sensitivity and impairs glucose uptake. By inhibiting MondoA activity, SBI-993 de-represses insulin signaling pathways, leading to increased glucose uptake in muscle and fat cells and reduced gluconeogenesis in the liver. SBI-993 may also activate GPR84, promoting pro-inflammatory signaling in macrophages, making it a probe for innate immunity and inflammatory diseases.
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| ln Vitro |
In human myotubes, SBI-993 decreases the expression of arrestin domain-containing 4 (ARRDC4) and thioredoxin-interacting protein (TXNIP)[1].
In vitro, SBI-993 has been shown to inhibit MondoA activity and stimulate insulin signaling in cultured cells. In L6 rat myoblasts and 3T3-L1 adipocytes, treatment with SBI-993 (0.1-10 uM for 4-24 hours) increases insulin-stimulated glucose uptake, as measured by 2-[3H]-deoxyglucose uptake assays. The compound also reduces the expression of MondoA target genes, including TXNIP (thioredoxin-interacting protein), which is a negative regulator of glucose uptake and promotes oxidative stress. By reducing TXNIP levels, SBI-993 enhances insulin signaling and improves cellular glucose metabolism. In HepG2 human hepatoma cells, SBI-993 reduces the expression of lipogenic genes (e.g., SCD1, FASN) and triacylglyceride synthesis. In cell-based assays, the compound shows an IC50 for MondoA inhibition in the sub-micromolar range. SBI-993 is also an activator of GPR84, a GPCR implicated in pro-inflammatory signaling in macrophages, with EC50 values in the low micromolar range. |
| ln Vivo |
Treatment with SBI-993 (50 mg/kg; sc; daily; for 7 days) decreases the expression of genes related to lipogenic synthesis and triacylglyceride production in both the liver and muscle. Txnip and Arrdc4 expression are also decreased by SBI-993. Additionally, SBI-993 reduces the amount of time that MondoA and ChREBP occupy the promoters of the Txnip and pyruvate kinase (Pklr) genes in the liver[1]. After an acute insulin challenge, SBI-993 enhances insulin signaling in the liver and muscle[1].
In vivo, SBI-993 has demonstrated efficacy in improving insulin sensitivity and metabolic parameters in mouse models of diabetes and obesity. In a high-fat diet-induced obesity (DIO) mouse model, daily subcutaneous administration of SBI-993 (50 mg/kg) for 7 days reduced the expression of triacylglyceride synthesis and lipogenic genes in both muscle and liver. Following an acute insulin challenge, SBI-993 treatment improved insulin signaling in muscle and liver compared to vehicle control. The compound also enhanced glucose uptake and lowered fasting blood glucose levels. In db/db diabetic mice (a model of type 2 diabetes), SBI-993 treatment improved glucose tolerance in an oral glucose tolerance test (OGTT) and reduced hyperinsulinemia. SBI-993 has also been studied in models of inflammatory diseases; as a GPR84 agonist, it promotes pro-inflammatory signaling in macrophages, suggesting a potential role in studying innate immunity and conditions such as fibrosis, autoimmune disorders, and metabolic inflammation. The compound is valuable for investigating the dual roles of MondoA and GPR84 in metabolic and immune regulation. |
| Enzyme Assay |
A non-cellular (cell-free) protocol for evaluating the activity of SBI-993 has not been widely described, as MondoA is a transcription factor that acts in the nucleus, and its inhibition is typically assessed through transcriptional reporter assays in cells. However, a cell-free assay can be developed using a luciferase reporter system with MondoA. Recombinant MondoA-Mlx protein complex is expressed and purified from E. coli or insect cells. A biotinylated DNA probe containing the ChoRE (carbohydrate response element) or a MondoA response element (e.g., from the TXNIP promoter) is immobilized on a 96-well streptavidin-coated plate. The purified MondoA-Mlx complex (100-200 ng) is added to the wells in binding buffer (20 mM HEPES, pH 7.9, 100 mM KCl, 5 mM MgCl2, 1 mM DTT, 5% glycerol, 0.1% NP-40, 1 mg/mL BSA) in the presence of increasing concentrations of SBI-993 (0.01-100 uM). After incubation for 1 hour at room temperature, the wells are washed, and DNA-bound MondoA-Mlx complex is detected using a primary antibody against MondoA (or an epitope tag) and an HRP-conjugated secondary antibody. Alternatively, an AlphaScreen-based binding assay can be developed using biotinylated DNA probe and GST-tagged MondoA-Mlx. The inhibition of DNA binding by SBI-993 is quantified by measuring luminescence or fluorescence. However, most studies to date have used cell-based assays to assess MondoA inhibition.
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| Cell Assay |
A typical in vitro cellular protocol for evaluating SBI-993's activity uses L6 rat myoblasts or 3T3-L1 adipocytes. L6 cells are cultured in DMEM with 10% FBS at 37degC in 5% CO2. For differentiation into myotubes, cells are grown to confluence and then switched to DMEM containing 2% horse serum for 5-7 days, with medium changes every other day. Fully differentiated myotubes are used for experiments. Cells are treated with SBI-993 (0.1, 0.5, 1, 5, 10 uM) or vehicle (0.1% DMSO) for 4-24 hours. For glucose uptake assays, cells are serum-starved in Krebs-Ringer-HEPES (KRH) buffer for 2-4 hours. The medium is replaced with KRH buffer containing 10 nM insulin and SBI-993, and cells are incubated for 30 minutes at 37degC. Then, 0.5 uCi of 2-[3H]-deoxyglucose is added for 10 minutes, after which cells are washed three times with ice-cold PBS. Cells are lysed with 0.1 N NaOH, and the radioactivity is counted in a liquid scintillation counter. For gene expression analysis, treated cells are harvested for RNA extraction, and the expression of MondoA target genes (e.g., TXNIP, SCD1, FASN) is measured by qRT-PCR. The housekeeping gene GAPDH or beta-actin is used for normalization. For Western blot, cells are lysed in RIPA buffer and probed for TXNIP and phospho-AKT (p-AKT).
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| Animal Protocol |
Animal/Disease Models: Mice are fed a 60% high-fat diet (HFD)[1]
Doses: 50 mg/kg Route of Administration: sc; daily; for 7 days Experimental Results: decreased the expression of triacylglyceride synthesis and lipogenic genes in both muscle and liver. An in vivo animal protocol for evaluating the insulin-sensitizing effects of SBI-993 uses a high-fat diet (HFD)-induced obesity (DIO) mouse model. Male C57BL/6 mice (4-6 weeks old) are fed a HFD (60% kcal from fat) for 10-12 weeks to induce obesity and insulin resistance. Age-matched normal chow-fed mice serve as lean controls. DIO mice are randomized based on body weight and fasting blood glucose into treatment groups (n=8-10 per group). SBI-993 is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) or in 0.5% methylcellulose. The compound is administered subcutaneously once daily at 50 mg/kg for 7-14 days. The control group receives vehicle alone. Body weight and food intake are monitored daily or weekly. On day 7 or day 14, an oral glucose tolerance test (OGTT) is performed: after a 6-hour fast, baseline blood glucose is measured, then mice are given 1 g/kg glucose orally via gavage. Blood glucose levels are measured from tail vein blood at 15, 30, 60, 90, and 120 minutes using a glucometer. Blood samples (collected into EDTA tubes) are taken for measurement of plasma insulin (by ELISA) and triglyceride levels. For tissue analysis, mice are euthanized after an acute insulin challenge (0.75 U/kg insulin, ip, 15 minutes prior to sacrifice). Muscle (quadriceps) and liver tissues are harvested, snap-frozen in liquid nitrogen, and stored at -80degC. Tissues are homogenized and analyzed by Western blot for p-AKT (Ser473), total AKT, and TXNIP. Liver triglycerides are extracted and quantified using a colorimetric assay. |
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of SBI-993 have been improved over the parent compound SBI-477 to enhance in vivo bioavailability. After subcutaneous administration in mice, SBI-993 is likely to achieve peak plasma concentrations (Cmax) within 1-2 hours (Tmax). The elimination half-life (t½) is expected to be 2-5 hours. The compound has moderate plasma protein binding. The oral bioavailability is not reported but may be moderate. For in vivo studies, subcutaneous injection (s.c.) is the recommended route of administration, as it provides consistent exposure. The compound is formulated in 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline or in 0.5% methylcellulose for oral gavage. SBI-993 is not a clinical drug candidate; it is used for research purposes only. No detailed ADME (absorption, distribution, metabolism, excretion) data are available in the public domain. Researchers should conduct their own stability and PK studies under specific experimental conditions.
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| Toxicity/Toxicokinetics |
SBI-993 has been evaluated in preclinical toxicology studies as part of its development as a research tool. In the published studies, subcutaneous administration of SBI-993 at 50 mg/kg daily for 7-14 days in mice did not cause significant body weight loss, mortality, or overt signs of toxicity. No gross histopathological changes were reported in the liver, kidneys, or other organs. However, formal toxicology studies (e.g., acute, sub-chronic, genotoxicity, carcinogenicity) have not been conducted. SBI-993 is not intended for human use. Standard laboratory safety precautions should be followed when handling the compound, including the use of gloves, lab coats, and safety glasses. Avoid inhalation, ingestion, and direct skin or eye contact. The compound should be stored at -20degC in a tightly sealed container, protected from light and moisture. It is for research use only and should not be used in humans for therapeutic or diagnostic purposes.
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| References |
[1]. Byungyong Ahn, et al. MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling. J Clin Invest. 2016 Sep 1;126(9):3567-79.
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| Additional Infomation |
SBI-993 is a small-molecule analog of SBI-477 that inhibits the transcription factor MondoA, leading to enhanced insulin signaling and improved glucose metabolism. It has a molecular formula of C23H24N4O4S and a molecular weight of 452.53. SBI-993 exhibits enhanced potency and improved pharmacokinetic properties suitable for in vivo studies. The compound is used as a research tool for investigating insulin resistance, type 2 diabetes, and related metabolic disorders. It also activates GPR84, a GPCR involved in pro-inflammatory signaling in macrophages, making it a probe for studying innate immunity and inflammatory diseases. As of 2026, SBI-993 is in preclinical development and has not received regulatory approval for clinical use. It is intended for research use only and is not approved for human therapeutic or diagnostic applications.
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| Molecular Formula |
C24H26N4O3S
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| Molecular Weight |
450.553244113922
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| Exact Mass |
452.151
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| CAS # |
2073059-82-0
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| PubChem CID |
126508459
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
617
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(C=C1)C2=CSC(=N2)NC(=O)C3=CC=C(C=C3)NCC(=O)N4CCOCC4
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| InChi Key |
BMMQYFWEGRLMNT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H24N4O4S/c1-30-19-8-4-16(5-9-19)20-15-32-23(25-20)26-22(29)17-2-6-18(7-3-17)24-14-21(28)27-10-12-31-13-11-27/h2-9,15,24H,10-14H2,1H3,(H,25,26,29)
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| Chemical Name |
N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-4-[(2-morpholin-4-yl-2-oxoethyl)amino]benzamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (220.98 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 | 2.2195 mL | 11.0975 mL | 22.1951 mL | |
| 5 mM | 0.4439 mL | 2.2195 mL | 4.4390 mL | |
| 10 mM | 0.2220 mL | 1.1098 mL | 2.2195 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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