Canagliflozin (JNJ 28431754)

Catalog No.S2760 Synonyms: TA 7284

For research use only.

Canagliflozin (TA 7284, JNJ 28431754) is a highly potent and selective SGLT2 inhibitor for hSGLT2 with IC50 of 2.2 nM in a cell-free assay, exhibits 413-fold selectivity over hSGLT1.

Canagliflozin (JNJ 28431754) Chemical Structure

CAS No. 842133-18-0

Selleck's Canagliflozin (JNJ 28431754) has been cited by 22 publications

Purity & Quality Control

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Biological Activity

Description Canagliflozin (TA 7284, JNJ 28431754) is a highly potent and selective SGLT2 inhibitor for hSGLT2 with IC50 of 2.2 nM in a cell-free assay, exhibits 413-fold selectivity over hSGLT1.
Targets
mSGLT2 [1]
(Cell-free assay)
rSGLT2 [1]
(Cell-free assay)
hSGLT2 [1]
(Cell-free assay)
2 nM 3.7 nM 4.4 nM
In vitro

Canagliflozin is a novel C-glucoside with thiophene ring. Canagliflozin inhibits Na+-dependent 14C-AMG uptake in a concentration-dependent fashion. Canagliflozin inhibits 14C-AMG uptake in CHO-hSGLT1 and mSGLT1 cells with IC50 of 0.7 μM and >1 μM, respectively. Canagliflozin inhibits the facilitative (non-Na+-linked) GLUT-mediated 2H-2-DG uptake in L6 myoblasts by less than 50%. In sham-injected oocytes, Canagliflozin (10 μM) or phlorizin (3 mM) alone in the presence of 50 μM DNJ does not affect currents. In SGLT3-injected oocytes, DMSO and Canagliflozin 10 μM inhibits DNJ-induced currents by 15.6% and 23.4%, respectively.[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHO NFTo[mtHfW6ldHnvckBie3OjeR?= M33yPFEzOCCvaX7z MUfJcohq[mm2aX;uJI9nKGi3bXHuJHNIVFR{IHX4dJJme3OnZDDpckBEUE9iY3XscJMh[XO|ZYPz[YQh[XNiZHXjdoVie2ViaX6geZB1[WunIH;mJHsyPEOfQV3HJIFnfGW{IEGyNEBucW6|IHL5JHRweEOxdX70JI1mfGixZDygTWM2OCB;IECuNFAzOiEQvF2u MlvNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NEe3PVEoRjJ6NES3O|kyRC:jPh?=
CHO M{fYfmZ2dmO2aX;uJIF{e2G7 Mo\CNVIxKG2rboO= NXXi[XlzUW6qaXLpeIlwdiCxZjDoeY1idiCVR1zUNUBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy|IHHzd4V{e2WmIHHzJIRm[3KnYYPlJIlvKHWydHHr[UBw\iCdMUTDYWFOTyCjZoTldkAyOjBibXnud{BjgSCWb4DDc5VvfCCvZYToc4QtKEmFNUCgQUAxNjJ4NTFOwG0v MoLTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NEe3PVEoRjJ6NES3O|kyRC:jPh?=
CHO-K1 NIPOSotHfW6ldHnvckBie3OjeR?= NGX0SIVKdmirYnn0bY9vKG:oIHj1cYFvKFOJTGSyJIV5eHKnc4Pl[EBqdiCFSF:tT|Eh[2WubIOgZpkhYzF2Q23BUWchfXC2YXvlJIF{e2G7LDDJR|UxKD1iMD6wNFY4KM7:TT6= MnTiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ4NUKyOVUoRjJ{NkWyNlU2RC:jPh?=
CHO-K1 MoTuSpVv[3Srb36gZZN{[Xl? MYrJcohq[mm2aX;uJI9nKGi3bXHuJHNIVFRzIHX4dJJme3OnZDDpckBEUE9vS{GgZ4VtdHNiYomgX|E1S12DTVegeZB1[WunIHHzd4F6NCCLQ{WwJF0hOS57IN88UU4> NVToU5BoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK2OVIzPTVpPkKyOlUzOjV3PD;hQi=>
Assay
Methods Test Index PMID
Western blot p-β-catenin / β-catenin / Cyclin D1 ; pACC / ACC / p-AMPKα / AMPKα / p-S6K / S6K / p-S6 / S6 31142735 27689018
In vivo Canagliflozin shows pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice. Oral administration at 30 mg/kg of Canagliflozin to male SD rats induces glucose excretion over 24 hours by 3,696 mg per 200 g body weight. Pharmacokinetic studies reveals a much higher exposure of Canagliflozin following oral administration. Following intravenous and oral doses of 3 and 10 mg/kg, respectively, to male SD rats, AUC0−inf, po, t1/2 and oral bioavailability are determined to be 35,980 ng·h/mL, 5.2 hours, and 85%, respectively. Thus, inhibition of SGLT2 in renal tubules after oral dosing of Canagliflozin is likely to continuously suppress reabsorption of glucose. The extensive UGE would reflect excellent pharmacokinetic properties of Canagliflozin in vivo as well as high potency of SGLT2 inhibition. Since most of the filtered glucose is reabsorbed by SGLT2 in the renal tubules, the novel compound would be useful for an anti-diabetic agent. Single oral administration of Canagliflozin at 3 mg/kg remarkably reduced blood glucose levels without influencing food intake in hyperglycemic high-fat diet fed KK (HF-KK) mice. There is a 48% reduction in blood glucose level versus vehicle at 6 hours. In contrast, Canagliflozin only slightly affects blood glucose levels in normoglycemic mice. Therefore, Canagliflozin would control hyperglycemia in the therapy of T2DM with low risk of hypoglycemia. [2]

Protocol (from reference)

Cell Research:[1]
  • Cell lines: L6 cell lines
  • Concentrations: 0-10 μM
  • Incubation Time: 24 hours
  • Method: 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.
Animal Research:[2]
  • Animal Models: KK (HF-KK) mice
  • Dosages: 10 mg/kg
  • Administration: Oral administration

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% CMC+0.25% Tween 80
For best results, use promptly after mixing.

18 mg/mL

Chemical Information

Molecular Weight 444.52
Formula

C24H25FO5S

CAS No. 842133-18-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(C=C(C=C1)C2C(C(C(C(O2)CO)O)O)O)CC3=CC=C(S3)C4=CC=C(C=C4)F

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04720859 Recruiting Drug: Canagliflozin 300 MG Oral Tablet Postprandial Hypoglycemia Hospital Universitari Vall d''Hebron Research Institute January 5 2018 Not Applicable
NCT02891954 Enrolling by invitation Drug: Canagliflozin Diabetes Mellitus Type 2 University of Maryland Baltimore|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) September 2016 Phase 1
NCT02737657 Completed -- Diabetes Mellitus Type 2 Janssen-Cilag International NV April 2016 --
NCT02857764 Completed -- Diabetes Mellitus Type 2 Janssen Research & Development LLC February 15 2016 --
NCT02688075 Completed Other: No Intervention Diabetes Mellitus Type 2 Janssen Inc. November 13 2015 --

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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