Details of the Drug

General Information of Drug (ID: DMFRM1I)

Drug Name
Canagliflozin
Synonyms
842133-18-0; Invokana; Canagliflozin anhydrous; canagliflozin hemihydrate; UNII-6S49DGR869; JNJ-28431754; JNJ 24831754ZAE; Canagliflozin hydrate; TA-7284; 1-(Glucopyranosyl)-4-methyl-3-(5-(4-fluorophenyl)-2-thienylmethyl)benzene; CHEBI:73274; 6S49DGR869; (2S,3R,4R,5S,6R)-2-(3-((5-(4-FLUOROPHENYL)THIOPHEN-2-YL)METHYL)-4-METHYLPHENYL)-6-(HYDROXYMETHYL)TETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; TA 7284; (1S)-1,5-anhydro-1-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucitol; 928672-86-0
Indication
Disease Entry ICD 11 Status REF
Non-insulin dependent diabetes 5A11 Approved [1]
Type-2 diabetes 5A11 Approved [2]
Diabetic nephropathy GB61.Z Phase 3 [3]
Type-1 diabetes 5A10 Phase 2 [4]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 444.5
Logarithm of the Partition Coefficient (xlogp) 3.2
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [5]
Bioavailability
The bioavailability of drug is 65% []
Clearance
The clearance of drug is 192 mL/min []
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 :Feces 41.5% as the unchanged radiolabeled drug7.0% as a hydroxylated metabolite3.2% 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 []
Half-life
The concentration or amount of drug in body reduced by one-half in 10.6 hours []
Metabolism
The drug is metabolized via O-glucuronidation []
Unbound Fraction
The unbound fraction of drug in plasma is 0.01% [6]
Vd
The volume of distribution (Vd) of drug is 83.5 L []
Chemical Identifiers
Formula
C24H25FO5S
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
Canonical SMILES
CC1=C(C=C(C=C1)[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)CC3=CC=C(S3)C4=CC=C(C=C4)F
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
InChIKey
XTNGUQKDFGDXSJ-ZXGKGEBGSA-N
Cross-matching ID
PubChem CID
24812758
ChEBI ID
CHEBI:73274
CAS Number
842133-18-0
DrugBank ID
DB08907
TTD ID
D08DFX
VARIDT ID
DR00279
INTEDE ID
DR0262
ACDINA ID
D00093
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Sodium/glucose cotransporter 2 (SGLT2) TTLWPVF SC5A2_HUMAN Modulator [7]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
UDP-glucuronosyltransferase 1A9 (UGT1A9)
Main DME 		DE85D2P UD19_HUMAN Substrate [10]
UDP-glucuronosyltransferase 2B4 (UGT2B4)
Main DME 		DENUPDX UD2B4_HUMAN Substrate [10]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Sodium/glucose cotransporter 2 (SLC5A2) OT93UUDI SC5A2_HUMAN Gene/Protein Processing [11]
UDP-glucuronosyltransferase 1A10 OTOTZVEY UD110_HUMAN Gene/Protein Processing [12]
UDP-glucuronosyltransferase 1A8 OTTMABBG UD18_HUMAN Gene/Protein Processing [12]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Canagliflozin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ripretinib DM958QB Moderate Decreased clearance of Canagliflozin due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [13]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium E00625 Not Available Disintegrant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Water E00035 962 Solvent
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Canagliflozin 100 mg tablet 100 mg Oral Tablet Oral
Canagliflozin 300 mg tablet 300 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Canagliflozin FDA Label
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4582).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
6 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
8 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.
9 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.
10 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.
11 Discovery of novel N--D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes. J Med Chem. 2011 Jan 13;54(1):166-78. doi: 10.1021/jm101072y. Epub 2010 Dec 3.
12 Evaluation of inhibitors of intestinal UDP-glucuronosyltransferases 1A8 and 1A10 using raloxifene as a substrate in Caco-2 cells: Studies with four flavonoids of Scutellaria baicalensis. Toxicol In Vitro. 2021 Apr;72:105087. doi: 10.1016/j.tiv.2021.105087. Epub 2021 Jan 10.
13 Cerner Multum, Inc. "Australian Product Information.".