Home GPCR & G Protein SGLT inhibitor Canagliflozin (JNJ 28431754) For research use only.

Canagliflozin (JNJ 28431754)

Synonyms: TA 7284

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

Canagliflozin (JNJ 28431754) Chemical Structure

CAS No. 842133-18-0

Purity & Quality Control

Canagliflozin (JNJ 28431754) Related Products

Signaling Pathway

SGLT Signaling Pathways

SGLT Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHO Function assay 120 mins Inhibition of human SGLT2 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method, IC50 = 0.0022 μM. 28447791
CHO Function assay 120 mins Inhibition of human SGLT1 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method, IC50 = 0.265 μM. 28447791
CHO-K1 Function assay Inhibition of human SGLT2 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 0.0067 μM. 22652255
CHO-K1 Function assay Inhibition of human SGLT1 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 1.9 μM. 22652255
Click to View More Cell Line Experimental Data

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
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 Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-β-catenin / β-catenin / Cyclin D1 pACC / ACC / p-AMPKα / AMPKα / p-S6K / S6K / p-S6 / S6 31142735
In Vivo
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]
Animal Research Animal Models KK (HF-KK) mice
Dosages 10 mg/kg
Administration Oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06301529 Enrolling by invitation
Healthy Aging
AgelessRx
 February 12 2024 Phase 4
NCT04720859 Unknown status
Postprandial Hypoglycemia
Hospital Universitari Vall d''Hebron Research Institute
 January 5 2018 Not Applicable
NCT02891954 Enrolling by invitation
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 --

Chemical Information & Solubility

Molecular Weight 444.52 Formula

C24H25FO5S
CAS No. 842133-18-0 SDF Download Canagliflozin (JNJ 28431754) SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 89 mg/mL ( (200.21 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Canagliflozin (JNJ 28431754) | Canagliflozin (JNJ 28431754) supplier | purchase Canagliflozin (JNJ 28431754) | Canagliflozin (JNJ 28431754) cost | Canagliflozin (JNJ 28431754) manufacturer | order Canagliflozin (JNJ 28431754) | Canagliflozin (JNJ 28431754) distributor