Canagliflozin

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Canagliflozin
Systematic (IUPAC) name
(2S,3R,4R,5S,6R)-2-{3-[5-[4-Fluoro-phenyl)-thiophen-2-ylmethyl]-4-methyl-phenyl}-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol
Clinical data
Pregnancy cat.C (US)
Legal status-only (US)
RoutesOral
Pharmacokinetic data
Bioavailability65%
Protein binding99%
MetabolismHepatic glucuronidation
Half-life10–13 hours
ExcretionFecal and renal
Identifiers
CAS number842133-18-0 YesY
ATC codeA10BX11
ChemSpider26333259 N
UNII6S49DGR869 N
ChEBICHEBI:73274 N
SynonymsJNJ-24831754; TA-7284; (1S)-1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol
Chemical data
FormulaC24H25FO5S 
Mol. mass444.52 g/mol
 N (what is this?)  (verify)
 
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Canagliflozin
Systematic (IUPAC) name
(2S,3R,4R,5S,6R)-2-{3-[5-[4-Fluoro-phenyl)-thiophen-2-ylmethyl]-4-methyl-phenyl}-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol
Clinical data
Pregnancy cat.C (US)
Legal status-only (US)
RoutesOral
Pharmacokinetic data
Bioavailability65%
Protein binding99%
MetabolismHepatic glucuronidation
Half-life10–13 hours
ExcretionFecal and renal
Identifiers
CAS number842133-18-0 YesY
ATC codeA10BX11
ChemSpider26333259 N
UNII6S49DGR869 N
ChEBICHEBI:73274 N
SynonymsJNJ-24831754; TA-7284; (1S)-1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol
Chemical data
FormulaC24H25FO5S 
Mol. mass444.52 g/mol
 N (what is this?)  (verify)

Canagliflozin (INN, trade name Invokana) is a drug for the treatment of type 2 diabetes.[1][2] It was developed by Mitsubishi Tanabe Pharma and is marketed under license by Janssen, a division of Johnson & Johnson.[3] Canagliflozin is an inhibitor of subtype 2 sodium-glucose transport protein (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine.[4]

In March 2013, canagliflozin became the first SGLT2 inhibitor to be approved in the United States.[5]

Side effects[edit]

Cardiovascular problems have been noted with this class of drugs along with canagliflozin. During one trial with canagliflozin there was an increased risk of stroke the individual MACE-plus component of stroke, the hazard ratio was non-significantly elevated, at 1.5 (95% CI, 0.8 - 2.6). Also the CANVAS trial, also with canagliflozin, showed some concern about cardiovascular events. Although final results from the CANVAS trial are not expected until 2015, during the first 30 days after randomization in CANVAS, there were 13 cardiovascular events in the patients receiving canagliflozin (0.45%) vs 1 in patients receiving placebo (0.07%). The hazard ratio of 6.5 was not significant because of the small number of events (95% confidence interval, 0.85 - 49.66).[6] Furthermore Johnson and Johnson also reported to investors that canagliflozin increased LDL cholesterol, urinary tract infections, genital mycotic infections, and was associated increased urination and episodes of hypotension and hypoglycemia. The same report did show that the drug decreased weight by a 1.9 - 3% (using the confidence intervals of the two studies sited) as well as decreased hemoglobin AIC by 0.57-0.70%, reduced both systolic and diastolic blood pressures[7] and raised HDL cholesterol.[3]

Status in other jurisdictions[edit]

On July 4, 2011, the European Medicines Agency approved a paediatric investigation plan and granted both a deferral and a waiver for canagliflozin (EMEA-001030-PIP01-10) in accordance with EC Regulation No.1901/2006 of the European Parliament and of the Council.[8]

References[edit]

  1. ^ New J&J diabetes drug effective in mid-stage study, Jun 26, 2010
  2. ^ Edward C. Chao (2011). "Canagliflozin". Drugs of the Future 36 (5): 351–357. doi:10.1358/dof.2011.36.5.1590789. 
  3. ^ a b http://www.investor.jnj.com/releasedetail.cfm?releaseid=710584
  4. ^ Prous Science: Molecule of the Month November 2007
  5. ^ "U.S. FDA approves Johnson & Johnson diabetes drug, canagliflozin". Reuters. Mar 29, 2013. "U.S. health regulators have approved a new diabetes drug from Johnson & Johnson, making it the first in its class to be approved in the United States." 
  6. ^ [1]
  7. ^ UEndocrine | SGLT2 inhibitors and blood pressure
  8. ^ "EMEA-001030-PIP01-10". EMA European Medicines Agency. Retrieved May 6, 2013.