KGA-2727

For research use only.

Catalog No.S8938

KGA-2727 Chemical Structure

CAS No. 666842-36-0

KGA-2727 is a potent, selective, high-affinity inhibitor of sodium glucose cotransporter 1 (SGLT1) with Ki of 97.4 nM and 43.5 nM for human SGLT1 and rat SGLT1, respectively. The selectivity ratios (Ki for SGLT2/Ki for SGLT1) of KGA-2727 are 140 (human) and 390 (rat). KGA-2727 exhibits antidiabetic efficacy in rodent models.

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Biological Activity

Description KGA-2727 is a potent, selective, high-affinity inhibitor of sodium glucose cotransporter 1 (SGLT1) with Ki of 97.4 nM and 43.5 nM for human SGLT1 and rat SGLT1, respectively. The selectivity ratios (Ki for SGLT2/Ki for SGLT1) of KGA-2727 are 140 (human) and 390 (rat). KGA-2727 exhibits antidiabetic efficacy in rodent models.
Targets
rat SGLT1 [1]
(Cell-free assay)
human SGLT1 [1]
(Cell-free assay)
43.5 nM(Ki) 97.4 nM(Ki)
In vitro

KGA-2727 inhibits SGLT1 potently and highly selectively in an in vitro assay using cells transiently expressing recombinant SGLTs.[1].

In vivo

In a small intestine closed loop absorption test with normal rats, KGA-2727 inhibits the absorption of glucose but not that of fructose. In the oral glucose tolerance test with streptozotocininduced diabetic rats, KGA-2727 attenuats the elevation of plasma glucose after glucose loading, indicating that KGA-2727 improves postprandial hyperglycemia. In Zucker diabetic fatty (ZDF) rats, chronic treatments with KGA-2727 reduces the levels of plasma glucose and glycated hemoglobin. Furthermore, KGA-2727 preserves glucose-stimulated insulin secretion and reduces urinary glucose excretion with improved morphological changes of pancreatic islets and renal distal tubules in ZDF rats. In addition, the chronic treatment with KGA-2727 increases the level of glucagon-like peptide-1 in the portal vein.[1].

Protocol

Cell Research:

[1]

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  • Cell lines: COS-7 cells
  • Concentrations: 0-1 μM, 0-100 μM
  • Incubation Time: --
  • Method:

    For the AMG uptake experiment, COS-7 cells are seeded into a 96-well collagen-coated culture plate at a density of 5 × 104 cells/well in Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum. After 4 h, each plasmid is transfected into COS-7 cells using Lipofectamine 2000 and the cells are used 2 days after transfection. In this experiment, AMG uptake at 0.3 or 1 mM is measured in the presence of various concentrations of KGA-2727 to calculate Ki values.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: Male Wistar, Zucker diabetic fatty (ZDF) fa/fa (ZDF/Gmi Crl-fa/fa), and ZDF-lean (ZDF/Gmi Crl-lean) rats
  • Dosages: 10 mg/kg, 30 mg/kg, 100 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (186.35 mM)
Water 100 mg/mL (186.35 mM)
Ethanol ''45 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 536.62
Formula

C26H40N4O8

CAS No. 666842-36-0
Storage powder
in solvent
Synonyms N/A
Smiles CC1=C(C=CC(=C1)OCCCNCCC(=O)N)CC2=C(NN=C2OC3C(C(C(C(O3)CO)O)O)O)C(C)C

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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SGLT Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID