LX-4211 (Synonyms: LP 802034, LX4211) |
| رقم الكتالوجGC15088 |
LX-4211 is an oral, potent dual SGLT2/1 inhibitor, with IC50 values of 36nM and 1.8nM for SGLT1 and SGLT2, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1018899-04-1
Sample solution is provided at 25 µL, 10mM.
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LX-4211 is an oral, potent dual SGLT2/1 inhibitor, with IC50 values of 36nM and 1.8nM for SGLT1 and SGLT2, respectively[1][2]. LX-4211 enhances urinary glucose excretion by inhibiting SGLT2 and reduces gastrointestinal glucose absorption by inhibiting SGLT1, thereby effectively lowering blood glucose levels[3][4]. LX-4211 is commonly used in diabetes-related research[5][6].
In vitro, treatment of porcine coronary artery cultured endothelial cells (ECs) with LX-4211 (10nM) for 30 minutes before the subsequent incubation in normo glucose or high glucose (HG: 25mmol/L) for 24 hours reduced glucose uptake stimulated by HG, and decreased ECs senescence markers and oxidative stress, upregulated eNOS expression and NO formation, and reduced the expression of VCAM-1, tissue factor, and the local angiotensin system[7].
In vivo, Oral treatment of nonobese diabetes-prone mice with cyclophosphamide-induced T1D with LX-4211(orally;2/30mg/kg/day)for 22 days significantly decreased blood glucose levels and A1c levels without increasing the rate of hypoglycemia measurements[8]. Oral administration of LX-4211 (60mg/kg)in mice reduces intestinal glucose absorption by inhibiting SGLT1, increases the release of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), while reducing the release of glucose-dependent insulinotropic polypeptide (GIP) and fluctuations in blood glucose levels during the 6 hours after a glucose-containing meal[4].
References:
[1] Zambrowicz, B., Freiman, J., Brown, P. M., Frazier, K. S., Turnage, A., Bronner, J., Ruff, D., Shadoan, M., Banks, P., Mseeh, F., Rawlins, D. B., Goodwin, N. C., Mabon, R., Harrison, B. A., Wilson, A., Sands, A., & Powell, D. R. (2012). LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clinical pharmacology and therapeutics, 92(2), 158–169.
[2] Goodwin, N. C., Ding, Z. M., Harrison, B. A., Strobel, E. D., Harris, A. L., Smith, M., Thompson, A. Y., Xiong, W., Mseeh, F., Bruce, D. J., Diaz, D., Gopinathan, S., Li, L., O'Neill, E., Thiel, M., Wilson, A. G., Carson, K. G., Powell, D. R., & Rawlins, D. B. (2017). Discovery of LX2761, a Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitor Restricted to the Intestinal Lumen, for the Treatment of Diabetes. Journal of medicinal chemistry, 60(2), 710–721.
[3] Goodwin, N. C., Mabon, R., Harrison, B. A., Shadoan, M. K., Almstead, Z. Y., Xie, Y., Healy, J., Buhring, L. M., DaCosta, C. M., Bardenhagen, J., Mseeh, F., Liu, Q., Nouraldeen, A., Wilson, A. G., Kimball, S. D., Powell, D. R., & Rawlins, D. B. (2009). Novel L-xylose derivatives as selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. Journal of medicinal chemistry, 52(20), 6201–6204.
[4] Powell, D. R., Smith, M., Greer, J., Harris, A., Zhao, S., DaCosta, C., Mseeh, F., Shadoan, M. K., Sands, A., Zambrowicz, B., & Ding, Z. M. (2013). LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose. The Journal of pharmacology and experimental therapeutics, 345(2), 250–259.
[5] Herat, L. Y., Matthews, J. R., Hibbs, M., Rakoczy, E. P., Schlaich, M. P., & Matthews, V. B. (2023). SGLT1/2 inhibition improves glycemic control and multi-organ protection in type 1 diabetes. iScience, 26(8), 107260.
[6] Bhatt, D. L., Szarek, M., Steg, P. G., Cannon, C. P., Leiter, L. A., McGuire, D. K., Lewis, J. B., Riddle, M. C., Voors, A. A., Metra, M., Lund, L. H., Komajda, M., Testani, J. M., Wilcox, C. S., Ponikowski, P., Lopes, R. D., Verma, S., Lapuerta, P., Pitt, B., & SOLOIST-WHF Trial Investigators (2021). Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. The New England journal of medicine, 384(2), 117–128.
[7] Khemais-Benkhiat, S., Belcastro, E., Idris-Khodja, N., Park, S. H., Amoura, L., Abbas, M., Auger, C., Kessler, L., Mayoux, E., Toti, F., & Schini-Kerth, V. B. (2020). Angiotensin II-induced redox-sensitive SGLT1 and 2 expression promotes high glucose-induced endothelial cell senescence. Journal of cellular and molecular medicine, 24(3), 2109–2122.
[8] Powell, D. R., Doree, D., Jeter-Jones, S., Ding, Z. M., Zambrowicz, B., & Sands, A. (2015). Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes. Diabetes, metabolic syndrome and obesity : targets and therapy, 8, 121–127.
| Cell experiment [1]: | |
Cell lines | Porcine coronary artery cultured endothelial cells (ECs) |
Preparation Method | Porcine hearts were collected from the local slaughterhouse. Left circumflex coronary arteries were excised, cleaned and flushed with PBS without calcium to remove remaining blood. For immunofluorescence staining, coronary artery segments with endothelium were incubated in RPMI containing a normal glucose concentration (NG: 11.1mmol/L) supplemented with fungizone (2.5μg/mL), penicillin (100U/mL), streptomycin (100μg/mL), HEPES (100mmol/L), in the absence or presence of empagliflozin (100nmol/L) or LX-4211(10nM) for 30 minutes before the subsequent incubation in normal glucose or high glucose (HG: 25mmol/L) for 24 hours. Thereafter, segments were washed with PBS before being embedded in FSC22 Frozen section medium and frozen in liquid nitrogen. |
Reaction Conditions | 10nM; 30min |
Applications | LX-4211 markedly reduced the level of oxidative stress in ECs. |
| Animal experiment [2]: | |
Animal models | Female NOD/ShiLtJ mice |
Preparation Method | Diabetic mice were randomized by body weight and blood glucose level into four treatment groups: 0.2U insulin/vehicle, 0.05U insulin/vehicle, 0.05U insulin/2mg/kg LX-4211 or 0.05U insulin/30mg/kg LX-4211. On day –1, while under isoflurane anesthesia, all mice were implanted subcutaneously with an Alzet micro-osmotic pump (model 1004, 4 weeks’ duration) delivering insulin in the form of Humulin R at doses of either 0.05U/day or 0.2U/day. On the next day (study day 1), all mice received their first daily dose of either vehicle (0.1% Tween 80 in water) alone or vehicle containing LX-4211, chemical structure (2S,3R,4R,5S,6R)-2-(4-chloro-3-[4-ethoxybenzyl] phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol. LX-4211 was delivered once in the afternoon by oral gavage at a dose of either 2mg/kg or 30mg/kg in a 10mL/kg total volume; these doses were chosen because in past mouse studies, 2mg/kg had a half-maximal effect and 30mg/kg a maximal effect on urinary glucose excretion. |
Dosage form | 2, 30mg/kg/day for 22 days; p.o. |
Applications | LX-4211(orally; 2/30mg/kg/day)for 22 days significantly decreased blood glucose levels and A1c levels without increasing the rate of hypoglycemia measurements. |
References: | |
| Cas No. | 1018899-04-1 | SDF | |
| المرادفات | LP 802034, LX4211 | ||
| Chemical Name | (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-trio | ||
| Canonical SMILES | CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)C3C(C(C(C(O3)SC)O)O)O)Cl | ||
| Formula | C21H25ClO5S | M.Wt | 424.94 |
| الذوبان | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS(pH 7.2) (1:1): 0.5 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3533 mL | 11.7664 mL | 23.5327 mL |
| 5 mM | 470.7 μL | 2.3533 mL | 4.7065 mL |
| 10 mM | 235.3 μL | 1.1766 mL | 2.3533 mL |
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Quality Control & SDS
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- Purity: >98.50%
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