| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
SGLT2
Luseogliflozin specifically targets the sodium-glucose co-transporter 2 (SGLT2), which is primarily expressed in the proximal tubule of the kidney. It is a selective potent and orally active second-generation SGLT2 inhibitor with an IC50 of 2.26 nM. By blocking SGLT2, it reduces renal glucose reabsorption, leading to increased urinary glucose excretion (UGE) and subsequently lowering plasma glucose concentrations. |
|---|---|
| ln Vitro |
Luseogliflozin can promote the growth of beta cells by stimulating the FoxM1/PLK1/CENP-A pathway through humoral factors that function independently of the insulin/IGF-1 receptor. In mice treated with OSI-906, levogliflozin promotes beta cell proliferation[2].
In vitro, Luseogliflozin hydrate is a selective and potent SGLT2 inhibitor (IC50 = 2.26 nM). It enhances beta cell proliferation by activating the FoxM1/PLK1/CENP-A pathway through signaling molecules that do not depend on the insulin/IGF-1 receptors. A cell viability assay conducted on betaIRKO, IRS1KO, and IRS2KO beta cells showed that serum from OSI-906 plus Luseogliflozin-treated groups significantly improved cell viability compared to the OSI-906 alone group. |
| ln Vivo |
In mice treated with OSI-906 (45 mg/kg), SGLT2 inhibition with Luseogliflozin (10 mg/kg/daily; oral gavage) effectively reduces hyperglycemia but not hyperinsulinemia. OSI-906-induced hyperglycemia is decreased by luseogliflozin[2].
In vivo, administration of Luseogliflozin (10 mg/kg/day; oral gavage) significantly ameliorates hyperglycemia, but not hyperinsulinemia, in OSI-906 (45 mg/kg)-treated mice. The treatment effectively mitigated the hyperglycemia provoked by OSI-906, demonstrating its therapeutic potential in ameliorating insulin receptor-independent hyperglycemia. Once-daily administration of Luseogliflozin for 7 days in clinical studies increased 24-hour UGE in a dose-dependent manner and reduced plasma glucose concentrations. |
| Enzyme Assay |
The specific in vitro protocol for SGLT2 inhibition uses a [14C]-methyl-alpha-D-glucopyranoside (AMG) uptake assay. Chinese hamster ovary (CHO) cells stably expressing human SGLT2 are seeded in 96-well plates at 1×10⁴ cells/well. Cells are washed with sodium-free buffer and pre-incubated with assay buffer (140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 5 mM Tris, pH 7.4) containing Luseogliflozin (0.01-1000 nM) for 15 minutes. [14C]-AMG is added to a final concentration of 100 uM and incubated for 30-60 minutes at 37degC. Cells are washed three times with ice-cold PBS, lysed with 0.2 N NaOH, and radioactivity is measured by liquid scintillation counting. IC50 is calculated from the concentration-response curve (IC50 = 2.26 nM).
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: βIRKO, IRS1KO and IRS2KO beta cells Tested Concentrations: 100 nM Incubation Duration: 24 and 48 hrs (hours) Experimental Results: Cell Viability Assay[2] Treating cells with serum from the OSI-906 (200 nM) or OSI-906+Luseogliflozin(100 nM) group led to Dramatically increased cell viability in the latter group in the control, IRS1KO, IRS2KO, as well as the insulin receptor (IR)-deficient βIRKO beta cells. For in vitro cellular assays evaluating beta cell proliferation, primary mouse pancreatic beta cells or MIN6 cells are isolated and cultured in 24-well plates. Cells are treated with serum from mice treated with OSI-906 (45 mg/kg) alone or OSI-906 plus Luseogliflozin (10 mg/kg/day) for 7 days. After 24-48 hours of culture, cell viability is measured using the MTT assay or CellTiter-Glo. Beta cell proliferation is assessed by immunostaining for Ki-67 and insulin. The serum from Luseogliflozin-treated groups significantly improves cell viability compared to the OSI-906 alone group, even in insulin receptor-deficient betaIRKO beta cells. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J male mice aged 8 weeks old[2]
Doses: 10 mg/kg/daily Route of Administration: Oral gavage; for 7 days between 08:00 and 09:00 hrs (hours) Experimental Results: Treatment Dramatically ameliorated the OSI-906 ( 45 mg/kg)-induced hyperglycaemia. An in vivo protocol for Luseogliflozin uses a mouse model of OSI-906-induced hyperglycemia. Male C57BL/6J mice (8 weeks old) are administered OSI-906 (45 mg/kg, an IGF-1R/insulin receptor inhibitor) daily to induce hyperglycemia. Luseogliflozin is administered concurrently via oral gavage at 10 mg/kg/day for 7 days. Blood glucose levels are measured daily using a glucometer. At the end of the study (day 7), serum insulin levels are measured by ELISA, and pancreatic islets are isolated for analysis of beta cell proliferation and gene expression. SGLT2 inhibition with Luseogliflozin effectively reduces hyperglycemia but not hyperinsulinemia, confirming its glucose-lowering mechanism independent of insulin. |
| ADME/Pharmacokinetics |
Luseogliflozin is well-tolerated and shows favorable pharmacokinetic (PK) and pharmacodynamic (PD) profiles in healthy male Japanese subjects. The observed and predicted PK for LUS have been characterized using a PBPK-UGE model in healthy and T2DM subjects after multiple ascending doses (MAD). A rapid LC-MS/MS method has been developed and validated for the quantitation of luseogliflozin in rat plasma for PK studies. Changes in luseogliflozin exposure in patients with mild and moderate hepatic impairment are minimal, with Cmax approximately 23% lower in patients with hepatic impairment compared to healthy subjects, but AUC is similar.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Luseogliflozin is not available. In clinical studies, luseogliflozin was well-tolerated in healthy male Japanese subjects and in patients with type 2 diabetes mellitus. Common adverse events associated with SGLT2 inhibitors include urinary tract infections, genital mycotic infections, and increased urination. Rare but serious adverse events include diabetic ketoacidosis and acute kidney injury. An LC-MS/MS method suitable for the quantitation of luseogliflozin in rat plasma has been validated for use in pharmacokinetic and pharmacodynamic/toxicodynamic studies in rats.
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| References | |
| Additional Infomation |
Luseogliflozin hydrate (brand name Lusefi) is an FDA- and PMDA-approved drug for the treatment of type 2 diabetes mellitus. Its molecular formula is C23H32O7S with a molecular weight of 452.56. It is a second-generation, selective, potent, and orally active SGLT2 inhibitor (IC50 = 2.26 nM). The compound increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway and is used in research on the role of SGLT2 inhibition in glucose homeostasis and diabetes complications.
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| Molecular Formula |
C23H32O7S
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|---|---|
| Molecular Weight |
452.56
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| Exact Mass |
452.186
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| CAS # |
1152425-66-5
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| Related CAS # |
Luseogliflozin;898537-18-3
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| PubChem CID |
56928196
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
|
| Complexity |
514
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O(C1C=C(C)C(CC2C=CC(OCC)=CC=2)=CC=1[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)S1)O)C.O
|
| InChi Key |
WKBFUVDLGJDBDP-NGOMLPPMSA-N
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| InChi Code |
InChI=1S/C23H30O6S.H2O/c1-4-29-16-7-5-14(6-8-16)10-15-11-17(18(28-3)9-13(15)2)23-22(27)21(26)20(25)19(12-24)30-23;/h5-9,11,19-27H,4,10,12H2,1-3H3;1H2/t19-,20-,21+,22-,23+;/m1./s1
|
| Chemical Name |
(2S,3R,4R,5S,6R)-2-[5-[(4-ethoxyphenyl)methyl]-2-methoxy-4-methylphenyl]-6-(hydroxymethyl)thiane-3,4,5-triol;hydrate
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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) |
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
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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 | 2.2097 mL | 11.0483 mL | 22.0965 mL | |
| 5 mM | 0.4419 mL | 2.2097 mL | 4.4193 mL | |
| 10 mM | 0.2210 mL | 1.1048 mL | 2.2097 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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