Remogliflozin (active form) is a potent and selective inhibitor of the low-affinity sodium glucose cotransporter 2 (SGLT2). Its inhibitory activity (Ki) against human SGLT2 is 12.4 ± 0.5 nM, and against human SGLT1 is 4520 ± 641 nM, resulting in a selectivity ratio (Ki SGLT1/Ki SGLT2) of 365. Against rat SGLT2, the Ki is 26.0 ± 2.4 nM, and against rat SGLT1, it is 997 ± 73 nM, resulting in a selectivity ratio of 38. [1]

The active metabolite, remogliflozin, potently and selectively inhibited sodium-dependent methyl-α-D-glucopyranoside (AMG) uptake in COS-7 cells transiently expressing human or rat SGLT2. The Ki values for human SGLT2 and rat SGLT2 were 12.4 nM and 26.0 nM, respectively. Its inhibitory effect on human SGLT1 was significantly weaker, with a Ki of 4520 nM. This demonstrates a high selectivity for SGLT2 over SGLT1. [1]

Remogliflozin etabonate (GSK189075; 10 or 30 mg/kg; oral; twice daily for 6 weeks) significantly reduces FPG and GHb levels in a dose-dependent manner [1]. Remogliflozin etabonate (3, 10, 30 mg/kg; oral) increases urinary glucose excretion in a dose-dependent manner. Remogliflozin etabonate dose-dependently inhibits the increase in plasma glucose and decreases plasma insulin after glucose load in normal rats [1]. Remogliflozin etabonate (1-10 mg/kg; oral) lowers blood glucose and reduces blood glucose AUC for 0-6 hours in a dose-dependent manner [1]. Remogliflozin etabonate (high-fat diet containing 0.01, 0.03 or 0.1% remogliflozin etabonate for 8 weeks) reduces plasma glucose, plasma insulin and GHb levels in a dose-dependent manner and inhibits the development of hypertriglyceridemia in male GK rats (6 weeks old) [1].

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Oral administration of remogliflozin etabonate to normal mice and rats resulted in a dose-dependent increase in 24-hour urinary glucose excretion. [1]
In a 16-hour fasted normal rat oral glucose tolerance test (2 g/kg glucose load), remogliflozin etabonate dose-dependently suppressed the postprandial increase in plasma glucose without stimulating insulin secretion. [1]
In streptozotocin-induced diabetic rats, remogliflozin etabonate significantly and dose-dependently inhibited the rise in plasma glucose following an oral glucose load, reducing the 0-2 hour area under the curve (AUC) for plasma glucose. The antihyperglycemic effect was more pronounced than in normal rats. [1]
In fed db/db mice, a single oral administration of remogliflozin etabonate (1-10 mg/kg) decreased blood glucose levels and reduced the 0-6 hour AUC for blood glucose in a dose-dependent manner. [1]
Chronic twice-daily oral administration of remogliflozin etabonate (10 or 30 mg/kg) to db/db mice for 6 weeks significantly reduced fasting plasma glucose and glycated hemoglobin (GHb) levels in a dose-dependent manner, inhibited the diabetes-associated decline in plasma insulin, suppressed the development of hypertriglyceridemia, and ameliorated glucosuria. [1]
In high-fat diet-fed Goto-Kakizaki (GK) rats, chronic dietary administration of remogliflozin etabonate (0.01%, 0.03%, or 0.1% in diet) for 8 weeks improved hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and insulin resistance. It reduced fasting plasma glucose and insulin levels, as well as the HOMA-R index, and reduced the AUCs for plasma glucose and insulin during an oral glucose tolerance test. [1]

Inhibitory Effects on Human and Rat SGLTs: COS-7 cells were seeded into 96-well collagen-coated plates. After 4 hours, the cells were transiently transfected with expression plasmids for human SGLT1, human SGLT2, rat SGLT1, or rat SGLT2. Two days post-transfection, the cells were used in a methyl-α-D-glucopyranoside (AMG) uptake assay. The AMG uptake experiment was performed using uptake buffer containing either 0.3 mM or 1 mM AMG. The Ki values for the test compounds against each SGLT were calculated from these uptake experiments. [1]

AMG Uptake Assay for SGLT Inhibition: COS-7 cells were seeded into 96-well collagen-coated plates and transiently transfected with human or rat SGLT1 or SGLT2 expression plasmids. Two days after transfection, the cells were used to assess the inhibitory effects of compounds on sodium-dependent methyl-α-D-glucopyranoside (AMG) uptake. The uptake buffer contained AMG at concentrations of 0.3 mM and 1 mM to calculate Ki values. The assay determined the concentration-dependent inhibition of AMG uptake by the compounds. [1]

Animal/Disease Models: 8weeks old db/db mice[1]
Doses: 10 or 30 mg/kg
Route of Administration: Oral; twice (two times) daily for 6 weeks
Experimental Results: Dramatically diminished fasting plasma glucose (FPG) in a dose-dependent manner and glycosylated hemoglobin (GHb) levels. Reduce urine output and urinary glucose excretion, and improve hyperglycemia.

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Urinary Glucose Excretion in Mice and Rats:** Remogliflozin etabonate was suspended in 0.5% sodium carboxymethylcellulose (CMC) and orally administered to female C57BL/6J mice (9 weeks old) and male Sprague-Dawley rats (7 weeks old). After administration, animals were placed in metabolic cages to collect urine for 24 hours. [1]
* **Oral Glucose Tolerance Test in Normal and STZ-Induced Diabetic Rats:** Male Sprague-Dawley rats (7 weeks old) or streptozotocin-induced diabetic Wistar rats were fasted for 16 hours. Remogliflozin etabonate (suspended in 0.5% CMC) was administered orally, followed by oral administration of a glucose solution (2 g/kg). Blood samples were collected from the tail vein at specified time points. [1]
* **Single Administration in db/db Mice:** Remogliflozin etabonate (suspended in 0.5% CMC) was orally administered to fed male db/db mice (10 weeks old). Blood samples were collected from the tail vein at specified time points. [1]
* **Chronic Administration in db/db Mice:** Remogliflozin etabonate (suspended in 0.1% methylcellulose) was orally administered to male db/db mice (8 weeks old) twice a day for 6 weeks. Body weight and food intake were measured every 2 weeks. Fasting blood samples were collected from the tail vein every 2 weeks. At the end of the treatment period, urine was collected over 24 hours using metabolic cages. [1]
* **Chronic Administration in High-Fat Diet-Fed GK Rats:** Male GK rats (6 weeks old) were fed a high-fat diet for 4 weeks to induce insulin resistance. They were then fed a high-fat diet containing 0.01%, 0.03%, or 0.1% remogliflozin etabonate for 8 weeks. Blood samples were collected from the tail vein from fed and fasted rats every 4 weeks to monitor parameters. An oral glucose tolerance test (1 g/kg glucose) was performed after 8 weeks of administration. [1]

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Urinary Glucose Excretion in Mice and Rats: Remogliflozin etabonate was suspended in 0.5% sodium carboxymethylcellulose (CMC) and orally administered to female C57BL/6J mice (9 weeks old) and male Sprague-Dawley rats (7 weeks old). After administration, animals were placed in metabolic cages to collect urine for 24 hours. [1]
Oral Glucose Tolerance Test in Normal and STZ-Induced Diabetic Rats: Male Sprague-Dawley rats (7 weeks old) or streptozotocin-induced diabetic Wistar rats were fasted for 16 hours. Remogliflozin etabonate (suspended in 0.5% CMC) was administered orally, followed by oral administration of a glucose solution (2 g/kg). Blood samples were collected from the tail vein at specified time points. [1]
Single Administration in db/db Mice: Remogliflozin etabonate (suspended in 0.5% CMC) was orally administered to fed male db/db mice (10 weeks old). Blood samples were collected from the tail vein at specified time points. [1]
Chronic Administration in db/db Mice: Remogliflozin etabonate (suspended in 0.1% methylcellulose) was orally administered to male db/db mice (8 weeks old) twice a day for 6 weeks. Body weight and food intake were measured every 2 weeks. Fasting blood samples were collected from the tail vein every 2 weeks. At the end of the treatment period, urine was collected over 24 hours using metabolic cages. [1]
Chronic Administration in High-Fat Diet-Fed GK Rats: Male GK rats (6 weeks old) were fed a high-fat diet for 4 weeks to induce insulin resistance. They were then fed a high-fat diet containing 0.01%, 0.03%, or 0.1% remogliflozin etabonate for 8 weeks. Blood samples were collected from the tail vein from fed and fasted rats every 4 weeks to monitor parameters. An oral glucose tolerance test (1 g/kg glucose) was performed after 8 weeks of administration. [1]

Remogliflozin etabonate is a prodrug. It is metabolized in the body to its active form, remogliflozin. [1]

Remogliflozin etabonate did not significantly alter plasma glucose levels in 16-hour fasted normal rats, suggesting a low risk of hypoglycemia. [1]

[1]. Remogliflozin Etabonate, in a Novel Category of Selective Low-Affinity Sodium Glucose Cotransporter (SGLT2) Inhibitors, Exhibits Antidiabetic Efficacy in Rodent Models. J Pharmacol Exp Ther. 2008 Oct;327(1):268-76.

Etaponin is a glycoside antibiotic. Etaponin has been used in clinical trials investigating type 2 diabetes and its basic science. Etaponin is an oral prodrug of repaggliflozin, a benzylpyrazole glucoside-based inhibitor of the renal sodium-glucose cotransporter 2 (SGLT2) with hypoglycemic activity. After administration and absorption, the inactive prodrug is converted to the active form repaggliflozin, which selectively acts on sodium-glucose cotransporter 2 (SGLT2).

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Remogliflozin etabonate is a novel category of selective SGLT2 inhibitors based on a benzylpyrazole glucoside scaffold. It was developed as an antidiabetic agent to promote urinary glucose excretion by inhibiting renal glucose reabsorption, thereby lowering blood glucose without stimulating insulin secretion. Its mechanism is independent of insulin, and it is hypothesized to prevent β-cell exhaustion by ameliorating hyperglycemia. [1]

C26H38N2O9

522.595

522.258

442201-24-3

Remogliflozin;329045-45-6

9871420

White to off-white solid powder

2.509

3

10

12

37

704

5

O1[C@H]([C@@H]([C@H]([C@@H]([C@H]1COC(=O)OCC)O)O)O)OC1C(CC2C=CC(=CC=2)OC(C)C)=C(C)N(C(C)C)N=1

UAOCLDQAQNNEAX-ABMICEGHSA-N

InChI=1S/C26H38N2O9/c1-7-33-26(32)34-13-20-21(29)22(30)23(31)25(36-20)37-24-19(16(6)28(27-24)14(2)3)12-17-8-10-18(11-9-17)35-15(4)5/h8-11,14-15,20-23,25,29-31H,7,12-13H2,1-6H3/t20-,21-,22+,23-,25+/m1/s1

ethyl [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[5-methyl-1-propan-2-yl-4-[(4-propan-2-yloxyphenyl)methyl]pyrazol-3-yl]oxyoxan-2-yl]methyl carbonate

GSK189075A GSK 189075A GSK-189075A

2934.99.9001

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, avoid exposure to moisture.

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

DMSO : ~100 mg/mL (~191.35 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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