Canagliflozin
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Identification
- Summary
Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used to manage hyperglycemia in type 2 diabetes mellitus (DM). Also used to reduce the risk of major cardiovascular events in patients with established cardiovascular disease and type 2 DM.
- Brand Names
- Invokamet, Invokana
- Generic Name
- Canagliflozin
- DrugBank Accession Number
- DB08907
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 444.516
Monoisotopic: 444.140672805 - Chemical Formula
- C24H25FO5S
- Synonyms
- Canagliflozin
- Canagliflozin anhydrous
- Canagliflozina
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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to prevent Cardiovascular mortality Combination Product in combination with: Metformin (DB00331) •••••••••••• ••••• •••••••• •••••••••••• •••• • •••••••• ••••••••• ••••••••••• •••••• Prevention of Cardiovascular mortality •••••••••••• ••••• •••••••••••• •••• • •••••••• ••••••••• •••••••• ••••••••••• •••••• Used in combination to prevent End stage renal disease (esrd) Combination Product in combination with: Metformin (DB00331) •••••••••••• ••••• •••• • •••••••• ••••••••• •••••••• •••••••••••• ••••••••••• •••••• Prevention of End stage renal disease (esrd) •••••••••••• ••••• •••• • •••••••• ••••••••• •••••••• •••••••••••• ••••••••••• •••••• Used in combination to prevent Hospitalizations Combination Product in combination with: Metformin (DB00331) •••••••••••• ••••• •••••••• •••••••••••• •••••••••••• •••• • •••••••• •••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.
Target Actions Organism ASodium/glucose cotransporter 2 inhibitorHumans - 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.
Hover over products below to view reaction partners
- 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.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Canagliflozin which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Abaloparatide is combined with Canagliflozin. Abametapir The serum concentration of Canagliflozin can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Canagliflozin. Abrocitinib The serum concentration of Canagliflozin can be increased when it is combined with Abrocitinib. - Food Interactions
- Avoid alcohol. Excess alcohol intake may promote ketoacidosis.
- Drink plenty of fluids.
- Take before a meal. It is recommended to take this drug before the first meal of the day.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Canagliflozin hydrate 0SAC974Z85 928672-86-0 VHOFTEAWFCUTOS-TUGBYPPCSA-N - Product Images
- Brand Name Prescription Products
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Invokamet Canagliflozin hydrate (50 mg/1) + Metformin hydrochloride (500 mg/1) Tablet, film coated Oral Janssen Pharmaceuticals 2014-08-08 Not applicable US Invokamet Canagliflozin hydrate (150 mg/1) + Metformin hydrochloride (500 mg/1) Tablet, film coated Oral Janssen Pharmaceuticals 2014-08-08 Not applicable US Invokamet Canagliflozin (50 mg) + Metformin hydrochloride (850 mg) Tablet Oral Janssen Pharmaceuticals 2016-06-28 2022-09-06 Canada Invokamet Canagliflozin (50 mg) + Metformin hydrochloride (1000 mg) Tablet Oral Janssen Pharmaceuticals 2016-06-28 Not applicable Canada Invokamet Canagliflozin hydrate (150 mg/1) + Metformin hydrochloride (1 g/1) Tablet, film coated Oral bryant ranch prepack 2014-08-08 Not applicable US
Categories
- ATC Codes
- A10BD16 — Metformin and canagliflozin
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Agents causing hyperkalemia
- Alimentary Tract and Metabolism
- Blood Glucose Lowering Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Diuretics
- Drugs that are Mainly Renally Excreted
- Drugs Used in Diabetes
- Glucosides
- Hypotensive Agents
- Oral Hypoglycemics
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
- Sulfur Compounds
- Thiophenes
- UGT1A9 Substrates
- Chemical TaxonomyProvided by Classyfire
- 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
- 2,5-disubstituted thiophene / Alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Benzenoid / C-glycosyl compound / Dialkyl ether / Ether / Fluorobenzene show 17 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, thiophenes, ring assembly, C-glycosyl compound (CHEBI:73274)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6S49DGR869
- CAS number
- 842133-18-0
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Steven L. Cowart and Max E. Stachura (1990). Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. (3rd ed.). Butterworths.
- 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]
- Diabetes, Heart Disease, and Stroke: NIDDK [Link]
- FDA Approved Drug Products: Invokana (canagliflozin) oral tablets [Link]
- FDA Approved Products: INVOKAMET (canagliflozin and metformin hydrochloride tablets), for oral use [Link]
- FDA Approved Drug Products: Invokana (canagliflozin) tablets for oral use (July 2023) [Link]
- Invokana, Canadian monograph [File]
- External Links
- KEGG Drug
- D09592
- PubChem Compound
- 24812758
- PubChem Substance
- 175427146
- ChemSpider
- 26333259
- BindingDB
- 50386885
- 1373458
- ChEBI
- 73274
- ChEMBL
- CHEMBL2048484
- ZINC
- ZINC000043207238
- PDBe Ligand
- L3R
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Canagliflozin
- PDB Entries
- 8hdh
- FDA label
- Download (687 KB)
- MSDS
- Download (24.7 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Cardiovascular Disease (CVD) / Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide Not Available Completed Not Available Diabetes 1 somestatus stop reason just information to hide Not Available Completed Not Available Type 2 Diabetes Mellitus 3 somestatus stop reason just information to hide Not Available Completed Treatment Fatty Liver Disease 1 somestatus stop reason just information to hide Not Available Completed Treatment Type 1 Diabetes Mellitus 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated Oral Tablet, extended release Oral Tablet, film coated, extended release Oral Tablet Oral 100 mg Tablet Oral 300 mg Tablet Oral 300.000 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 300 mg/1 Tablet, film coated Oral 100 mg Tablet, film coated Oral 300 mg Tablet, coated Oral Tablet, film coated Oral 150.00 mg Tablet, film coated Oral 50.00 mg Tablet, coated Oral 100 mg Tablet, coated Oral 300 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6723340 No 2004-04-20 2021-10-25 US US8222219 No 2012-07-17 2024-07-30 US US8513202 No 2013-08-20 2027-12-03 US US7943582 No 2011-05-17 2029-02-26 US US8785403 No 2014-07-22 2024-07-30 US US7943788 No 2011-05-17 2027-07-14 US US10617668 No 2020-04-14 2031-05-11 US US11576894 No 2010-07-06 2030-07-06 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 68-72 https://www.trc-canada.com/product-detail/?CatNum=C175190 boiling point (°C) 642.9±55.0 http://www.chemspider.com/Chemical-Structure.26333259.html water solubility almost insoluble https://www.ema.europa.eu/en/documents/assessment-report/invokana-epar-public-assessment-report_en.pdf logP 3.44 https://www.tga.gov.au/file/824/download pKa 13.34 https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2103841/ - Predicted Properties
Property Value Source Water Solubility 0.0045 mg/mL ALOGPS logP 3.09 ALOGPS logP 3.52 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 12.57 Chemaxon pKa (Strongest Basic) -3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 90.15 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 116.14 m3·mol-1 Chemaxon Polarizability 46.64 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9541 Blood Brain Barrier + 0.7708 Caco-2 permeable - 0.6554 P-glycoprotein substrate Substrate 0.6058 P-glycoprotein inhibitor I Non-inhibitor 0.8414 P-glycoprotein inhibitor II Non-inhibitor 0.9447 Renal organic cation transporter Non-inhibitor 0.8544 CYP450 2C9 substrate Non-substrate 0.6853 CYP450 2D6 substrate Non-substrate 0.8293 CYP450 3A4 substrate Non-substrate 0.5929 CYP450 1A2 substrate Non-inhibitor 0.6579 CYP450 2C9 inhibitor Non-inhibitor 0.6178 CYP450 2D6 inhibitor Non-inhibitor 0.8683 CYP450 2C19 inhibitor Non-inhibitor 0.5958 CYP450 3A4 inhibitor Non-inhibitor 0.7086 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7691 Ames test Non AMES toxic 0.584 Carcinogenicity Non-carcinogens 0.9103 Biodegradation Not ready biodegradable 0.9936 Rat acute toxicity 2.5975 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9912 hERG inhibition (predictor II) Non-inhibitor 0.7246
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0110900000-6c638b8cc9b7c8253bc1 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-05fr-0010900000-780b01732bb78212c604 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0059-0293500000-971fac7697402f469e04 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4l-6329400000-05216d0f205e9b7873c0 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01pk-1195400000-ed127b8052948e8ac04c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4l-4349000000-4f678932f3ddaddb0cdb Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 200.55614 predictedDeepCCS 1.0 (2019) [M+H]+ 202.45152 predictedDeepCCS 1.0 (2019) [M+Na]+ 208.35258 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity)
- Specific Function
- alpha-glucoside transmembrane transporter activity
- Gene Name
- SLC5A2
- Uniprot ID
- P31639
- Uniprot Name
- Sodium/glucose cotransporter 2
- Molecular Weight
- 72895.995 Da
References
- 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. [Article]
- FDA label, Invokana [File]
- Invokana, Canadian monograph [File]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- Sarnoski-Brocavich S, Hilas O: Canagliflozin (invokana), a novel oral agent for type-2 diabetes. P T. 2013 Nov;38(11):656-66. [Article]
- 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. [Article]
- FDA label, Invokana [File]
- Invokana, Canadian monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18719240, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18719240, PubMed:23288867). Catalyzes the glucuronidation of the endogenous estrogen hormones such as estradiol and estriol (PubMed:18719240, PubMed:23288867)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B4
- Uniprot ID
- P06133
- Uniprot Name
- UDP-glucuronosyltransferase 2B4
- Molecular Weight
- 60512.035 Da
References
- Sarnoski-Brocavich S, Hilas O: Canagliflozin (invokana), a novel oral agent for type-2 diabetes. P T. 2013 Nov;38(11):656-66. [Article]
- 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. [Article]
- FDA label, Invokana [File]
- Invokana, Canadian monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Functions as a 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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
- FDA label, Invokana [File]
- Invokana, Canadian monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- Invokana, Canadian monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Invokana, Canadian monograph [File]
Drug created at June 17, 2013 06:21 / Updated at October 29, 2024 14:47