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Canagliflozin (JNJ 28431754) SGLT2 Inhibitor

Name: Canagliflozin (JNJ 28431754)
Brand: Selleck Chemicals
SKU: S2760
Availability: InStock
Rating: 5 (34 reviews)

Cat.No.S2760

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.

Chemical Structure

Molecular Weight: 444.52

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.92%

99.92

Related Targets	Adrenergic Receptor AChR 5-HT Receptor Histamine Receptor Dopamine Receptor Ras GPR GluR Prostaglandin Receptor CXCR Adenosine Receptor P2 Receptor CCR Angiotensin Receptor Hedgehog/Smoothened S1P Receptor PKA Cannabinoid Receptor cAMP Glucagon Receptor Opioid Receptor Sigma Receptor PAR Endothelin Receptor LTR Neurokinin Receptor Guanylate Cyclase PKG LPA Receptor OX Receptor
Related Products	Sotagliflozin Phlorizin Phloretin (RJC 02792) Tofogliflozin(CSG 452) Ipragliflozin L-Proline Ipragliflozin (ASP1941) Swertisin KGA-2727 Mizagliflozin (KWA 0711) Bexagliflozin (EGT1442)

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	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

Chemical Information, Storage & Stability

Molecular Weight	444.52	Formula	C₂₄H₂₅FO₅S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	842133-18-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	TA 7284			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

Solubility

In vitro
Batch:

DMSO : 89 mg/mL (200.21 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.000mg/ml (6.75mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.500mg/ml (3.37mM)	Taking the 1 mL working solution as an example, add 50 μL of 30 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.

Mechanism of Action

Targets/IC₅₀/Ki	mSGLT2 ^[1] (Cell-free assay) 2 nM rSGLT2 ^[1] (Cell-free assay) 3.7 nM hSGLT2 ^[1] (Cell-free assay) 4.4 nM
In vitro	Canagliflozin (JNJ 28431754) is a novel C-glucoside with thiophene ring. It inhibits Na⁺-dependent ¹⁴C-AMG uptake in a concentration-dependent fashion. This compound inhibits ¹⁴C-AMG uptake in CHO-hSGLT1 and mSGLT1 cells with IC50 of 0.7 μM and >1 μM, respectively. It 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]
In vivo	Canagliflozin (JNJ 28431754) shows pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice. Oral administration at 30 mg/kg of this compound 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 following oral administration. Following intravenous and oral doses of 3 and 10 mg/kg, respectively, to male SD rats, AUC_0−inf, po, t_1/2 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 is likely to continuously suppress reabsorption of glucose. The extensive UGE would reflect excellent pharmacokinetic properties 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 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, it 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]
References	[1] https://pubmed.ncbi.nlm.nih.gov/22355316/ [2] https://pubmed.ncbi.nlm.nih.gov/20690635/

Applications

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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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	--

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