General
Preferred name
CANAGLIFLOZIN
Synonyms
JNJ 24831754ZAE (hemihydrate) ()
JNJ 28431754AAA (hemihydrate) ()
TA 7284 (hemihydrate) ()
CANAGLIFLOZIN HYDRATE ()
JNJ 28431754 ()
JNJ 28431754AAA ()
TA 7284 ()
JNJ 24831754ZAE ()
JNJ28431754 hemihydrate ()
TA-7284 hemihydrate ()
Canagliflozin D4 ()
CANAGLIFLOZIN ANHYDROUS ()
Canagliflozin hemihydrate ()
Canagliflozin (hemihydrate) ()
JNJ 28431754 (hemihydrate) ()
Canagliflozin (JNJ 28431754) ()
JNJ-28431754 ()
JNJ-28431754-AAA ()
JNJ-24831754-ZAE ()
TA-7284 ()
Canagliflozin ()
Invokana ()
Canagliflozin hydrate ()
Canagliflozin ()
Canagliflozin-d4 ()
P&D ID
PD000132
CAS
928672-86-0
842133-18-0
1997338-61-0
Tags
natural product
drug
available
Approved by
PMDA
EMA
FDA
First approval
2013
2011
Drug Status
approved
Drug indication
Diabetic nephropathy
Type-2 diabetes
Type-1 diabetes
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ABSORPTION
**Bioavailability and steady-state**; ; The absolute oral bioavailability of canagliflozin, on average, is approximately 65% [FDA label]. Steady-state concentrations are achieved after 4 to 5 days of daily dose administration between the range of 100mg to 300mg [FDA 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 [FDA label].
PHARMACODYNAMICS
This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent manner [FDA label]. The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine [A176969, T545]. 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 [A177086, L5933]. 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 [A177095].;
MOA
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 [FDA label].
INDICATION
This drug is used in conjunction with diet and exercise to increase glycemic control in adults diagnosed with type 2 diabetes mellitus [FDA label].; ; Another indication for canagliflozin is for the prevention of major cardiovascular events (myocardial infarction, stroke, or death due to a cardiovascular cause) in patients with type 2 diabetes [FDA label], [L5897].; ; It is important to note that this drug is **not** indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis [FDA label].
ROE
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 [FDA 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.
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 [FDA 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 [FDA Label]. There are known risks, however, of uncontrolled diabetes in pregnancy [FDA 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 [FDA 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 [FDA 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 [FDA label].
METABOLISM
Canagliflozin is primarily metabolized by O-glucuronidation. It is mainly glucuronidated by UGT1A9 and UGT2B4 enzymes to two inactive O-glucuronide metabolites [FDA Label].; ; The oxidative metabolism of canagliflozin by hepatic cytochrome enzyme CYP3A4 is negligible (about 7%) in humans [FDA label].
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 [FDA label].
DESCRIPTION
Marketed formulations may contain canagliflozin in a hemihydrate form (PubChem CID 24997615).
(GtoPdb)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
23
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
50
Molecular Weight
444.14
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
4
Rotatable Bonds
5
Ring Count
4
Aromatic Ring Count
3
cLogP
2.97
TPSA
90.15
Fraction CSP3
0.33
Chiral centers
5.0
Largest ring
6.0
QED
0.49
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
GPCR/G protein
Membrane Transporter/Ion Channel
Target
hSGLT2
mSGLT2
rSGLT2
SGLT
SLC5A1, SLC5A2
SGLT2 inhibitor
Indication
diabetes mellitus
MOA
sodium/glucose cotransporter inhibitor
Source data
