Canagliflozin

SKU: orb1307458

Description

Canagliflozin is a potent and selective SGLT2 inhibitor with IC50 values of 2, 3.7, and 4.4 nM against mouse, rat, and human SGLT2, respectively. It is widely used in research for type 2 diabetes, enabling in vitro transport assays and in vivo studies of glycemic control and renal function.

Research Area

Cell Biology

Key Properties

• CAS Number: 842133-18-0
• MW: 444.5
• Purity: >98%
• Formula: C₂₄H₂₅FO₅S
• SMILES: O[C@H]1[C@@H](O[C@H](CO)[C@@H](O)[C@@H]1O)C2=CC(CC=3SC(=CC3)C4=CC=C(F)C=C4)=C(C)C=C2
• Target: Glucose transporter
• Solubility: Soluble in DMSO (up to 40 mg/ml)

Bioactivity

• Target IC50:
  SGLT2 (mouse):2 nM|14C-AMG uptake:684 ± 159 nM (CHO-hSGLT1 cells)|SGLT2 (human):4.4 nM|SGLT2 (rat):3.7 nM
• In Vivo:
  METHODS: To study the efficacy of treatment of type 2 diabetes mellitus (T2DM), Canagliflozin (0.1-30 mg/kg, 0.5% hydroxypropyl methylcellulose) was administered by gavage to four animal models. The animal models included: (1) male C57BL/6J mice fed a high-fat diet; (2) male C57BL/ksj-db/db hyperglycemic mice; (3) male Zucker fatty (ZF) obese, insulin-resistant rats; and (4) male ZDF obese, hyperglycemic rats. RESULTS: Canagliflozin decreased RTG and increased UGE, improved glycemic control and β-cell function, and reduced body weight gain in a rodent model of T2DM.
• In Vitro:
  METHODS: CHOK-hSGLT1 and CHOK-hSGLT2 cells were incubated with Canagliflozin (0.01-10000 nM) for 10 min and sodium-dependent glucose uptake was detected. RESULTS: Canagliflozin inhibited 14C-AMG uptake in CHO-hSGLT1 and CHOK-hSGLT2 cells with IC50 of 684±159 nM and 4.4±1.2 nM, respectively. METHODS: Human umbilical vein endothelial cell HUVECs were treated with Canagliflozin (1-50 µM) for 24 h and DNA synthesis was measured to monitor cell proliferation. RESULTS: Treatment of HUVECs with Canagliflozin resulted in a concentration-dependent inhibition of DNA synthesis. The ability of Canagliflozin to block DNA synthesis was observed at concentrations (5-10 µM) achieved in the plasma of patients receiving Canagliflozin. In addition, higher concentrations of Canagliflozin (50 µM) virtually eliminated DNA synthesis.
• Cell Research:
  Cells from the rat skeletal muscle cell line, L6, is used to test the effect of Canagliflozin on glucose transporter 1 (GLUT1) activity. Cells are maintained in Dulbecco's modified Eagle's medium containing 5.6 mM glucose supplemented with 10% fetal bovine serum, are seeded in 24-well plates at a density of 3 × 105 cells/well and cultured for 24 hours in an atmosphere of 5% CO2 at 37 °C. Cells are rinsed twice with Kreb's ringer phosphate HEPES buffer (pH 7.4, 150 mM NaCl, 5 mM KCl, 1.25 mM MgSO4, 1.25 mM CaCl2, 2.9 mM Na2HPO4, 10 mM HEPES) and are pre-incubated with the solutions of Canagliflozin (250 μL, 10 μM) for 5 minutes at room temperature. The transport reaction is initiated by adding 50 μL of 4.5 mM 2-DG (a substrate for GLUTs)/3H-2-DG (0.625 μCi) followed by incubation for 15 minutes at room temperature. The 2-DG uptake is halted by aspiration of the incubation mixture. Cells are immediately washed 3 times with ice-cold PBS. Samples are extracted with 0.3 N NaOH, and radioactivity is determined by liquid scintillation.(Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

JNJ-24831754

Compound Identifiers

PubChem CID

24812758