Identification

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Name
Canagliflozin
Accession Number
DB08907
Type
Small Molecule
Groups
Approved
Description

Canagliflozin, also known as Invokana, is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the management of type 2 diabetes mellitus along with lifestyle changes including diet and exercise Label.

It was initially approved by the FDA in 2013 for the management of diabetes and later approved in 2018 for a second indication of reducing the risk of cardiovascular events in patients diagnosed with type 2 diabetes mellitus 8, Label.

Canagliflozin is the first oral antidiabetic drug approved for the prevention of cardiovascular events in patients with type 2 diabetes 8. Cardiovascular disease is the most common cause of death in these patients 4.

Structure
Thumb
Synonyms
  • Canagliflozin
  • Canagliflozin anhydrous
  • Canagliflozina
Product Ingredients
IngredientUNIICASInChI Key
Canagliflozin hydrate0SAC974Z85928672-86-0VHOFTEAWFCUTOS-TUGBYPPCSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InvokanaTablet, film coated100 mg/1OralJanssen Pharmaceuticals, Inc.2013-03-29Not applicableUs50458 0140 90 nlmimage10 4744a395
InvokanaTablet, film coated300 mg/1OralA-S Medication Solutions2013-03-29Not applicableUs
InvokanaTablet300 mgOralJanssen Pharmaceuticals2014-05-28Not applicableCanada
InvokanaTablet, film coated300 mg/1Oral.Cardinal Health2013-03-29Not applicableUs
InvokanaTablet100 mgOralJanssen Pharmaceuticals2014-06-03Not applicableCanada
InvokanaTablet, film coated100 mg/1Oral.Cardinal Health2013-03-29Not applicableUs
InvokanaTablet, film coated300 mg/1OralJanssen Pharmaceuticals, Inc.2013-03-29Not applicableUs50458 0141 30 nlmimage10 a344d186
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
InvokametCanagliflozin (50 mg) + Metformin hydrochloride (500 mg)TabletOralJanssen Pharmaceuticals2016-06-28Not applicableCanada
InvokametCanagliflozin hydrate (150 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coatedOralJanssen Pharmaceuticals, Inc.2014-08-08Not applicableUs
InvokametCanagliflozin hydrate (150 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralJanssen Pharmaceuticals, Inc.2014-08-08Not applicableUs
InvokametCanagliflozin (150 mg) + Metformin hydrochloride (1000 mg)TabletOralJanssen Pharmaceuticals2016-06-28Not applicableCanada
InvokametCanagliflozin hydrate (50 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coatedOralJanssen Pharmaceuticals, Inc.2014-08-08Not applicableUs
InvokametCanagliflozin (150 mg) + Metformin hydrochloride (850 mg)TabletOralJanssen Pharmaceuticals2016-06-28Not applicableCanada
InvokametCanagliflozin (150 mg) + Metformin hydrochloride (500 mg)TabletOralJanssen Pharmaceuticals2016-06-28Not applicableCanada
InvokametCanagliflozin hydrate (50 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralJanssen Pharmaceuticals, Inc.2014-08-08Not applicableUs
InvokametCanagliflozin (50 mg) + Metformin hydrochloride (850 mg)TabletOralJanssen Pharmaceuticals2016-06-28Not applicableCanada
InvokametCanagliflozin (50 mg) + Metformin hydrochloride (1000 mg)TabletOralJanssen Pharmaceuticals2016-06-28Not applicableCanada
Categories
UNII
6S49DGR869
CAS number
842133-18-0
Weight
Average: 444.516
Monoisotopic: 444.140672805
Chemical Formula
C24H25FO5S
InChI Key
XTNGUQKDFGDXSJ-ZXGKGEBGSA-N
InChI
InChI=1S/C24H25FO5S/c1-13-2-3-15(24-23(29)22(28)21(27)19(12-26)30-24)10-16(13)11-18-8-9-20(31-18)14-4-6-17(25)7-5-14/h2-10,19,21-24,26-29H,11-12H2,1H3/t19-,21-,22+,23-,24+/m1/s1
IUPAC Name
(2S,3R,4R,5S,6R)-2-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)-6-(hydroxymethyl)oxane-3,4,5-triol
SMILES
[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1

Pharmacology

Indication

This drug is used in conjunction with diet and exercise to increase glycemic control in adults diagnosed with type 2 diabetes mellitus Label.

Another indication for canagliflozin is the prevention of major cardiovascular events (myocardial infarction, stroke, or death due to a cardiovascular cause) in patients with type 2 diabetes, as well as hospitalization for heart failure in patients with type 2 diabetes8,10.

In addition to the above, canagliflozin can be used to lower the risk of end-stage kidney disease and major increases in serum creatinine and cardiovascular death for patients with a combination of type 2 diabetes mellitus, diabetic nephropathy, and albuminuria.10

It is important to note that this drug is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis Label.

Associated Conditions
Associated Therapies
Pharmacodynamics

This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent manner Label. The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine 2,7. The end result of canagliflozin administration is increased urinary excretion of glucose and less renal absorption of glucose, decreasing glucose concentration in the blood and improving glycemic control.

A note on type 2 diabetes and cardiovascular disease

The risk of cardiovascular events in diabetes type 2 is increased due to the damaging effects of diabetes on blood vessels and nerves in the cardiovascular system. In particular, there is a tendency for hyperglycemia to create pro-atherogenic (plaque forming) lesions in blood vessels, leading to various fatal and non-fatal events including stroke and myocardial infarction 5,9. Long-term glycemic control has been proven to be effective in the prevention of cardiovascular events such as myocardial infarction and stroke in patients with type 2 diabetes 6.

Mechanism of action

The sodium-glucose co-transporter2 (SGLT2), is found in the proximal tubules of the kidney, and reabsorbs filtered glucose from the renal tubular lumen. Canagliflozin inhibits the SGLT2 co-transporter. This inhibition leads to lower reabsorption of filtered glucose into the body and decreases the renal threshold for glucose (RTG), leading to increased glucose excretion in the urine Label.

TargetActionsOrganism
ASodium/glucose cotransporter 2
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Bioavailability and steady-state

The absolute oral bioavailability of canagliflozin, on average, is approximately 65% Label. Steady-state concentrations are achieved after 4 to 5 days of daily dose administration between the range of 100mg to 300mg Label.

Effect of food on absorption

Co-administration of a high-fat meal with canagliflozin exerted no appreciable effect on the pharmacokinetic parameters of canagliflozin. This drug may be administered without regard to food. Despite this, because of the potential of canagliflozin to decrease postprandial plasma glucose excretion due to prolonged intestinal glucose absorption, it is advisable to take this drug before the first meal of the day Label.

Volume of distribution

This drug is extensively distributed throughout the body. On average, the volume of distribution of canagliflozin at steady state following a single intravenous dose in healthy patients was measured to be 83.5 L Label.

Protein binding

Canagliflozin is mainly bound to albumin. The plasma protein binding of this drug is 99% Label.

Metabolism

Canagliflozin is primarily metabolized by O-glucuronidation. It is mainly glucuronidated by UGT1A9 and UGT2B4 enzymes to two inactive O-glucuronide metabolites Label.

The oxidative metabolism of canagliflozin by hepatic cytochrome enzyme CYP3A4 is negligible (about 7%) in humans Label.

Route of elimination

After a single oral radiolabeled dose canagliflozin dose to healthy subjects, the following ratios of canagliflozin or metabolites were measured in the feces and urine Label:

Feces

41.5% as the unchanged radiolabeled drug

7.0% as a hydroxylated metabolite

3.2% as an O-glucuronide metabolite

Urine

About 33% of the ingested radiolabled dose was measured in the urine, generally in the form of O-glucuronide metabolites. Less than 1% of the dose was found excreted as unchanged drug in urine.

Half life

In a clinical study, the terminal half-life of canagliflozin was 10.6 hours for the 100mg dose and 13.1 hours for the 300 mg dose Label.

Clearance

In healthy subjects, canagliflozin clearance was approximately 192 mL/min after intravenous (IV) administration Label.

The renal clearance of 100 mg and 300 mg doses of canagliflozin was measured to be in the range of 1.30 - 1.55 mL/min Label.

Toxicity

Overdose information

If an overdose occurs, contact the Poison Control Center. Normal supportive measures should be taken, including the removal unabsorbed drug from the gastrointestinal tract, initiating clinical monitoring of the patient, and providing supportive treatment as deemed necessary. Canagliflozin has been removed in very small quantities after a 4-hour hemodialysis session. This drug is likely not dialyzable by peritoneal dialysis Label.

Pregnancy and lactation

Animal data has demonstrated that canagliflozin may cause adverse renal effects in a growing fetus. Data are insufficient at this time in determining a potential canagliflozin related risk for major birth defects or possible miscarriage in humans Label. There are known risks, however, of uncontrolled diabetes in pregnancy Label. Inform female patients taking canagliflozin of the potential risk, which is increased during the second and third trimesters. This drug is not recommended during nursing Label.

Mutagenesis and carcinogenicity

Canagliflozin was not found to be mutagenic in both metabolically activated and inactivated states in the Ames assay. Canagliflozin showed mutagenicity in laboratory mouse lymphoma assay, but only in the activated state. Canagliflozin was not found to be mutagenic in several in vivo assays performed on rats Label.

The carcinogenic risk of canagliflozin was assessed in 2-year studies completed in both CD1 mice and Sprague-Dawley rats. Canagliflozin was not shown to increase tumor incidence in mouse models given doses less than or equal to 14 times the exposure from a typical 300 mg dose in humans. Despite these negative findings in mice, the incidence of several tumors increased in mice, including Leydig cell tumors, renal tubular adenomas, and adrenal pheochromocytomas Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
2,4-thiazolidinedioneCanagliflozin may increase the hypoglycemic activities of 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Canagliflozin can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the orthostatic hypotensive activities of Canagliflozin.
AbacavirAbacavir may decrease the excretion rate of Canagliflozin which could result in a higher serum level.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Canagliflozin.
AcarboseCanagliflozin may increase the hypoglycemic activities of Acarbose.
AcebutololThe therapeutic efficacy of Acebutolol can be increased when used in combination with Canagliflozin.
AceclofenacAceclofenac may decrease the excretion rate of Canagliflozin which could result in a higher serum level.
AcemetacinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Acemetacin.
AcetaminophenThe serum concentration of Canagliflozin can be increased when it is combined with Acetaminophen.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Lamos EM, Younk LM, Davis SN: Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013 Jun;9(6):763-75. doi: 10.1517/17425255.2013.791282. Epub 2013 Apr 17. [PubMed:23590413]
  2. Osaki A, Okada S, Saito T, Yamada E, Ono K, Niijima Y, Hoshi H, Yamada M: Renal threshold for glucose reabsorption predicts diabetes improvement by sodium-glucose cotransporter 2 inhibitor therapy. J Diabetes Investig. 2016 Sep;7(5):751-4. doi: 10.1111/jdi.12473. Epub 2016 Feb 16. [PubMed:27181936]
  3. Deeks ED, Scheen AJ: Canagliflozin: A Review in Type 2 Diabetes. Drugs. 2017 Sep;77(14):1577-1592. doi: 10.1007/s40265-017-0801-6. [PubMed:28836175]
  4. Joseph JJ, Golden SH: Type 2 diabetes and cardiovascular disease: what next? Curr Opin Endocrinol Diabetes Obes. 2014 Apr;21(2):109-20. doi: 10.1097/MED.0000000000000044. [PubMed:24569552]
  5. Gleissner CA, Galkina E, Nadler JL, Ley K: Mechanisms by which diabetes increases cardiovascular disease. Drug Discov Today Dis Mech. 2007;4(3):131-140. doi: 10.1016/j.ddmec.2007.12.005. [PubMed:18695749]
  6. Mannucci E, Dicembrini I, Lauria A, Pozzilli P: Is glucose control important for prevention of cardiovascular disease in diabetes? Diabetes Care. 2013 Aug;36 Suppl 2:S259-63. doi: 10.2337/dcS13-2018. [PubMed:23882055]
  7. Steven L. Cowart and Max E. Stachura (1990). Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. (3rd ed.). Butterworths.
  8. U.S. FDA Approves INVOKANA® (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease [Link]
  9. Diabetes, Heart Disease, and Stroke: NIDDK [Link]
  10. Invokana FDA label [Link]
  11. Invokana, Canadian monograph [File]
External Links
KEGG Drug
D09592
PubChem Compound
24812758
PubChem Substance
175427146
ChemSpider
26333259
BindingDB
50386885
ChEBI
73274
ChEMBL
CHEMBL2048484
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Canagliflozin
ATC Codes
A10BD16 — Metformin and canagliflozinA10BK02 — Canagliflozin
AHFS Codes
  • 68:20.18 — Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
FDA label
Download (687 KB)
MSDS
Download (24.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers7
1CompletedNot AvailableHealthy Volunteers / Hepatic Insufficiency1
1CompletedOtherDiabetes Mellitus (DM) / Fibroblast Growth Factor (FGF23) / Healthy Volunteers / Phosphate / PTH / Vitamin D1
1CompletedOtherHealthy Volunteers2
1CompletedTreatmentBioequivalence1
1CompletedTreatmentHealthy Volunteers31
1CompletedTreatmentHealthy Volunteers / Impaired kidney function1
1CompletedTreatmentPlasma Volume / Type 2 Diabetes Mellitus1
1CompletedTreatmentType 2 Diabetes Mellitus7
1Enrolling by InvitationBasic ScienceType 2 Diabetes Mellitus1
1, 2CompletedTreatmentType 2 Diabetes Mellitus1
1, 2Not Yet RecruitingTreatmentBreast Cancer / Colo-rectal Cancer / Endometrial Cancer / Head and Neck Carcinoma / Lung Cancers1
2CompletedTreatmentBMI >30 kg/m22
2CompletedTreatmentDiabetes Mellitus, Non Insulin Dependent / Type 2 Diabetes Mellitus1
2CompletedTreatmentType 1 Insulin-Dependent Diabetes Mellitus1
2CompletedTreatmentType 2 Diabetes Mellitus1
3CompletedTreatmentCardiovascular Heart Disease / Risk Factors / Type 2 Diabetes Mellitus1
3CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
3CompletedTreatmentDiabetic Nephropathies / Type 2 Diabetes Mellitus1
3CompletedTreatmentType 2 Diabetes Mellitus14
3CompletedTreatmentImpaired kidney function / Type 2 Diabetes Mellitus1
3RecruitingTreatmentDiabetic Nephropathies1
3RecruitingTreatmentType 2 Diabetes Mellitus1
4Active Not RecruitingBasic ScienceDiabetes Mellitus (DM) / Gouty Arthritis / Hyperuricemia1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
4CompletedTreatmentAlbuminuria / Type 2 Diabetes Mellitus1
4CompletedTreatmentBMI >27 kg/m2 / BMI >30 kg/m2 / Type 2 Diabetes Mellitus1
4CompletedTreatmentHeart Failure, Systolic / Type 2 Diabetes Mellitus1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentType 2 Diabetes Mellitus6
4RecruitingTreatmentChronic Kidney Disease (CKD) / Type 2 Diabetes Mellitus1
4RecruitingTreatmentDiabetic Nephropathies / Type 2 Diabetes Mellitus1
4RecruitingTreatmentType 2 Diabetes Mellitus3
4RecruitingTreatmentType II Diabetes in Subjects BMI 27 to 32 / Type II Diabetes in the Not so Obese1
4TerminatedTreatmentBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
4WithdrawnBasic ScienceCardiovascular Heart Disease / Type2 Diabetes Mellitus1
4WithdrawnTreatmentDiabetes, Obesity1
Not AvailableActive Not RecruitingNot AvailableDiabetes Mellitus (DM)1
Not AvailableActive Not RecruitingNot AvailableType 2 Diabetes Mellitus1
Not AvailableActive Not RecruitingTreatmentType 1 Insulin-Dependent Diabetes Mellitus1
Not AvailableCompletedNot AvailableCardiovascular Heart Disease / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus2
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus1
Not AvailableRecruitingOtherArterial Hypertension / Type 2 Diabetes Mellitus / Weight Changes1
Not AvailableWithdrawnBasic ScienceHeart Failure / Type2 Diabetes1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral
TabletOral100 mg
TabletOral300 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral300 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6723340No2004-04-202021-10-25Us
US8222219No2012-07-172024-07-30Us
US8513202No2013-08-202027-12-03Us
US7943582No2011-05-172029-02-26Us
US8785403No2014-07-222024-07-30Us
US7943788No2011-05-172027-07-14Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)68-72https://www.trc-canada.com/product-detail/?CatNum=C175190
boiling point (°C) ‎642.9±55.0http://www.chemspider.com/Chemical-Structure.26333259.html
water solubilityalmost insolublehttps://www.ema.europa.eu/en/documents/assessment-report/invokana-epar-public-assessment-report_en.pdf
logP3.44https://www.tga.gov.au/file/824/download
pKa13.34https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2103841/
Predicted Properties
PropertyValueSource
Water Solubility0.0045 mg/mLALOGPS
logP3.09ALOGPS
logP3.52ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)12.57ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area90.15 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity116.14 m3·mol-1ChemAxon
Polarizability46.5 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9541
Blood Brain Barrier+0.7708
Caco-2 permeable-0.6554
P-glycoprotein substrateSubstrate0.6058
P-glycoprotein inhibitor INon-inhibitor0.8414
P-glycoprotein inhibitor IINon-inhibitor0.9447
Renal organic cation transporterNon-inhibitor0.8544
CYP450 2C9 substrateNon-substrate0.6853
CYP450 2D6 substrateNon-substrate0.8293
CYP450 3A4 substrateNon-substrate0.5929
CYP450 1A2 substrateNon-inhibitor0.6579
CYP450 2C9 inhibitorNon-inhibitor0.6178
CYP450 2D6 inhibitorNon-inhibitor0.8683
CYP450 2C19 inhibitorNon-inhibitor0.5958
CYP450 3A4 inhibitorNon-inhibitor0.7086
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7691
Ames testNon AMES toxic0.584
CarcinogenicityNon-carcinogens0.9103
BiodegradationNot ready biodegradable0.9936
Rat acute toxicity2.5975 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9912
hERG inhibition (predictor II)Non-inhibitor0.7246
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenolic glycosides. These are organic compounds containing a phenolic structure attached to a glycosyl moiety. Some examples of phenolic structures include lignans, and flavonoids. Among the sugar units found in natural glycosides are D-glucose, L-Fructose, and L rhamnose.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Phenolic glycosides
Alternative Parents
Hexoses / C-glycosyl compounds / Toluenes / Fluorobenzenes / 2,5-disubstituted thiophenes / Oxanes / Aryl fluorides / Heteroaromatic compounds / Secondary alcohols / Polyols
show 5 more
Substituents
Phenolic glycoside / Hexose monosaccharide / C-glycosyl compound / 2,5-disubstituted thiophene / Toluene / Fluorobenzene / Halobenzene / Aryl fluoride / Aryl halide / Monocyclic benzene moiety
show 17 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, thiophenes, ring assembly, C-glycosyl compound (CHEBI:73274)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Low-affinity glucose:sodium symporter activity
Specific Function
Sodium-dependent glucose transporter. Has a Na(+) to glucose coupling ratio of 1:1.Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capac...
Gene Name
SLC5A2
Uniprot ID
P31639
Uniprot Name
Sodium/glucose cotransporter 2
Molecular Weight
72895.995 Da
References
  1. Lamos EM, Younk LM, Davis SN: Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013 Jun;9(6):763-75. doi: 10.1517/17425255.2013.791282. Epub 2013 Apr 17. [PubMed:23590413]
  2. FDA label, Invokana [File]
  3. Invokana, Canadian monograph [File]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Sarnoski-Brocavich S, Hilas O: Canagliflozin (invokana), a novel oral agent for type-2 diabetes. P T. 2013 Nov;38(11):656-66. [PubMed:24391386]
  2. Devineni D, Vaccaro N, Murphy J, Curtin C, Mamidi RN, Weiner S, Wang SS, Ariyawansa J, Stieltjes H, Wajs E, Di Prospero NA, Rothenberg P: Effects of rifampin, cyclosporine A, and probenecid on the pharmacokinetic profile of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants. Int J Clin Pharmacol Ther. 2015 Feb;53(2):115-28. doi: 10.5414/CP202158. [PubMed:25407255]
  3. FDA label, Invokana [File]
  4. Invokana, Canadian monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Sarnoski-Brocavich S, Hilas O: Canagliflozin (invokana), a novel oral agent for type-2 diabetes. P T. 2013 Nov;38(11):656-66. [PubMed:24391386]
  2. Devineni D, Vaccaro N, Murphy J, Curtin C, Mamidi RN, Weiner S, Wang SS, Ariyawansa J, Stieltjes H, Wajs E, Di Prospero NA, Rothenberg P: Effects of rifampin, cyclosporine A, and probenecid on the pharmacokinetic profile of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants. Int J Clin Pharmacol Ther. 2015 Feb;53(2):115-28. doi: 10.5414/CP202158. [PubMed:25407255]
  3. FDA label, Invokana [File]
  4. Invokana, Canadian monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Mosley JF 2nd, Smith L, Everton E, Fellner C: Sodium-Glucose Linked Transporter 2 (SGLT2) Inhibitors in the Management Of Type-2 Diabetes: A Drug Class Overview. P T. 2015 Jul;40(7):451-62. [PubMed:26185406]
  2. FDA label, Invokana [File]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Lamos EM, Younk LM, Davis SN: Canagliflozin , an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013 Jun;9(6):763-75. doi: 10.1517/17425255.2013.791282. Epub 2013 Apr 17. [PubMed:23590413]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Mamidi RNVS, Dallas S, Sensenhauser C, Lim HK, Scheers E, Verboven P, Cuyckens F, Leclercq L, Evans DC, Kelley MF, Johnson MD, Snoeys J: In vitro and physiologically-based pharmacokinetic based assessment of drug-drug interaction potential of canagliflozin. Br J Clin Pharmacol. 2017 May;83(5):1082-1096. doi: 10.1111/bcp.13186. Epub 2016 Dec 20. [PubMed:27862160]
  2. Devineni D, Vaccaro N, Murphy J, Curtin C, Mamidi RN, Weiner S, Wang SS, Ariyawansa J, Stieltjes H, Wajs E, Di Prospero NA, Rothenberg P: Effects of rifampin, cyclosporine A, and probenecid on the pharmacokinetic profile of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants. Int J Clin Pharmacol Ther. 2015 Feb;53(2):115-28. doi: 10.5414/CP202158. [PubMed:25407255]
  3. FDA label, Invokana [File]
  4. Invokana, Canadian monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Invokana, Canadian monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Invokana, Canadian monograph [File]

Drug created on June 17, 2013 00:21 / Updated on December 08, 2019 20:10