Identification

Name
Dapagliflozin
Accession Number
DB06292
Type
Small Molecule
Groups
Approved
Description

Dapagliflozin is indicated for the management of diabetes mellitus type 2, and functions to improve glycemic control in adults when combined with diet and exercise. Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor, which prevents glucose reabsorption in the kidney. Using dapagliflozin leads to heavy glycosuria (glucose excretion in the urine), which can lead to weight loss and tiredness. Dapagliflozin was approved by the FDA on Jan 08, 2014. Dapagliflozin is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Structure
Thumb
Synonyms
  • (2S,3R,4R,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)phenyl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
External IDs
BMS 512148 / BMS-512148
Product Ingredients
IngredientUNIICASInChI Key
Dapagliflozin propanediol monohydrate887K2391VH960404-48-2GOADIQFWSVMMRJ-UPGAGZFNSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EdistrideTablet, film coated5 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated10 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated10 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated5 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated5 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated10 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated10 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated5 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated10 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
EdistrideTablet, film coated5 mgOralAstra Zeneca Ab2015-11-09Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
QternDapagliflozin (10 mg) + Saxagliptin (5 mg)TabletOralAstra ZenecaNot applicableNot applicableCanada
QternDapagliflozin (10 mg/1) + Saxagliptin hydrochloride (5 mg/1)Tablet, film coatedOralAstra Zeneca Lp2017-12-04Not applicableUs
QternDapagliflozin (5 mg) + Saxagliptin (5 mg)TabletOralAstra ZenecaNot applicableNot applicableCanada
XigduoDapagliflozin propanediol monohydrate (5 mg) + Metformin Hydrochloride (1000 mg)Tablet, film coatedOralAstra Zeneca Ab2014-01-16Not applicableEu
XigduoDapagliflozin (5 mg) + Metformin Hydrochloride (850 mg)TabletOralAstra Zeneca2016-02-08Not applicableCanada
XigduoDapagliflozin propanediol monohydrate (5 mg) + Metformin Hydrochloride (1000 mg)Tablet, film coatedOralAstra Zeneca Ab2014-01-16Not applicableEu
XigduoDapagliflozin propanediol monohydrate (5 mg) + Metformin Hydrochloride (850 mg)Tablet, film coatedOralAstra Zeneca Ab2014-01-16Not applicableEu
XigduoDapagliflozin propanediol monohydrate (5 mg) + Metformin Hydrochloride (850 mg)Tablet, film coatedOralAstra Zeneca Ab2014-01-16Not applicableEu
XigduoDapagliflozin propanediol monohydrate (5 mg) + Metformin Hydrochloride (1000 mg)Tablet, film coatedOralAstra Zeneca Ab2014-01-16Not applicableEu
XigduoDapagliflozin propanediol monohydrate (5 mg) + Metformin Hydrochloride (1000 mg)Tablet, film coatedOralAstra Zeneca Ab2014-01-16Not applicableEu
Categories
UNII
1ULL0QJ8UC
CAS number
461432-26-8
Weight
Average: 408.873
Monoisotopic: 408.133966239
Chemical Formula
C21H25ClO6
InChI Key
JVHXJTBJCFBINQ-ADAARDCZSA-N
InChI
InChI=1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1
IUPAC Name
(2S,3R,4R,5S,6R)-2-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-6-(hydroxymethyl)oxane-3,4,5-triol
SMILES
CCOC1=CC=C(CC2=C(Cl)C=CC(=C2)[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C1

Pharmacology

Indication

Dapagliflozin is indicated for adjunct management of glycemic control in patients with type 2 diabetes mellitus, in combination with diet and exercise.

Associated Conditions
Pharmacodynamics

Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients with type 2 diabetes mellitus following the administration of dapagliflozin. A Dapagliflozin dose of 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day at week 12. A near maximum glucose excretion was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin also results in increases in urinary volume.

Mechanism of action

A competitive inhibitor of the sodium-glucose transport subtype 2 protein, dapagliflozin blocks glucose reabsorption into the kidney, resulting in the elimination of blood glucose through the urine.

TargetActionsOrganism
ASodium/glucose cotransporter 2
antagonist
inhibitor
Human
Absorption

Cmax is about 1 hour. (Obtained from 6 adult men in a fasted state administered a 50mg dose). 1.6% of unchanged dapagliflozin was found in the urine. A high-fat meal (52% caloric content) had no significant effect on previous pharmacokinetic parameters.

Volume of distribution
Not Available
Protein binding

91%.

Metabolism

Dapagliflozin 3-O-glucuronide is the primary metabolite of dapagliflozin, with 61% of the dapagliflozin dose recovered in the urine as this metabolite. The metabolism of dapagliflozin is primarily mediated by UGT1A9-dependent glucuronide conjugation. The major metabolite, dapagliflozin 3-O-glucuronide, is not an SGLT2 inhibitor.

Route of elimination
Not Available
Half life

13.8 hours with the consumption of a 50 mg dose.

Clearance

Oral plasma clearance of 4.9 mL/min/kg, and a renal clearance of 5.6 mL/min.

Toxicity

Compared to placebo-treated patients, patients with moderate renal impairment treated with dapagliflozin did not have improvement in glycemic control and had more renal-related adverse reactions and more bone fractures; therefore, dapagliflozin should not be initiated in this population. Based on its mechanism of action, dapagliflozin is not expected to be effective in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) or ESRD.

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

Interactions

Drug Interactions
DrugInteraction
2,4-thiazolidinedioneDapagliflozin may increase the hypoglycemic activities of 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Dapagliflozin can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AbemaciclibThe serum concentration of Dapagliflozin can be increased when it is combined with Abemaciclib.
AbirateroneThe metabolism of Dapagliflozin can be decreased when combined with Abiraterone.
AcarboseDapagliflozin may increase the hypoglycemic activities of Acarbose.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Dapagliflozin.
AcemetacinThe therapeutic efficacy of Dapagliflozin can be decreased when used in combination with Acemetacin.
AcetaminophenThe serum concentration of Dapagliflozin can be increased when it is combined with Acetaminophen.
AcetazolamideThe therapeutic efficacy of Dapagliflozin can be increased when used in combination with Acetazolamide.
AcetohexamideDapagliflozin may increase the hypoglycemic activities of Acetohexamide.
Food Interactions
Not Available

References

General References
  1. Obermeier M, Yao M, Khanna A, Koplowitz B, Zhu M, Li W, Komoroski B, Kasichayanula S, Discenza L, Washburn W, Meng W, Ellsworth BA, Whaley JM, Humphreys WG: In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010 Mar;38(3):405-14. doi: 10.1124/dmd.109.029165. Epub 2009 Dec 8. [PubMed:19996149]
  2. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
  3. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, Imai Y, Boulton DW: Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab. 2011 Apr;13(4):357-65. doi: 10.1111/j.1463-1326.2011.01359.x. [PubMed:21226818]
External Links
KEGG Drug
D08897
PubChem Compound
9887712
PubChem Substance
175427068
ChemSpider
8063384
BindingDB
50448923
ChEBI
85078
ChEMBL
CHEMBL429910
Drugs.com
Drugs.com Drug Page
Wikipedia
Dapagliflozin
ATC Codes
A10BX09 — DapagliflozinA10BD15 — Metformin and dapagliflozinA10BD21 — Saxagliptin and dapagliflozin
AHFS Codes
  • 68:20.18 — Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
FDA label
Download (868 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentType 2 Diabetes Mellitus2
1CompletedNot AvailableDiabetes Mellitus (DM) / Healthy Male and Female Subjects1
1CompletedNot AvailableType 2 Diabetes Mellitus9
1CompletedBasic ScienceDiabetes, Diabetes Mellitus Type 11
1CompletedBasic ScienceHealthy Volunteers4
1CompletedBasic ScienceType 2 Diabetes Mellitus2
1CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentType 2 Diabetes Mellitus7
1CompletedTreatmentType1diabetes1
1RecruitingBasic ScienceHealthy Volunteers1
1TerminatedNot AvailableType 2 Diabetes Mellitus1
1TerminatedDiagnosticDiabetes, NOS1
2CompletedBasic SciencePhysical Activity1
2CompletedBasic ScienceType 2 Diabetes Mellitus1
2CompletedTreatmentAsymptomatic Hyperuricemia1
2CompletedTreatmentBMI >30 kg/m21
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
2CompletedTreatmentT2 Diabetes and Fatty Liver Disease (Non-alcoholic Origin)1
2CompletedTreatmentType 2 Diabetes Mellitus4
2Not Yet RecruitingTreatmentDiabetes, Diabetes Mellitus Type 1 / Hypoglycemia / Hypoglycemia Unawareness1
2RecruitingBasic ScienceMetabolically Healthy Controls / Type 2 Diabetes Mellitus1
2RecruitingBasic ScienceObese experiencing rapid weight loss1
2RecruitingPreventionBMI >30 kg/m2 / Prediabetic State1
2RecruitingPreventionChronic Kidney Disease (CKD) / Proteinuria1
2RecruitingPreventionDiabetes, Diabetes Mellitus Type 11
2TerminatedBasic ScienceObese experiencing rapid weight loss1
2, 3CompletedTreatmentType 2 Diabetes Mellitus2
2, 3CompletedTreatmentType 2 Diabetes Mellitus, CKD and Albuminuria / Type 2 Diabetes Mellitus, CKD3 and Albuminuria1
3Active Not RecruitingTreatmentChronic Heart Failure With Reduced Ejection Fraction (HFrEF)1
3Active Not RecruitingTreatmentDiabetes Mellitus (DM)1
3Active Not RecruitingTreatmentDiabetes Prevention in Women After GDM Who Are at High-risk1
3Active Not RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
3CompletedTreatmentCardiovascular Disease (CVD) / High Blood Pressure (Hypertension) / Inadequate Glycaemic Control / Type 2 Diabetes Mellitus1
3CompletedTreatmentCardiovascular Disease (CVD) / Inadequate Glycaemic Control / Type 2 Diabetes Mellitus1
3CompletedTreatmentDiabetes Mellitus (DM)2
3CompletedTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 11
3CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent / High Risk for Cardiovascular Event1
3CompletedTreatmentDiabetes, Diabetes Mellitus Type 12
3CompletedTreatmentHigh Blood Sugar / Type 2 Diabetes Mellitus1
3CompletedTreatmentHigh Blood Sugar / Type2 Diabetes1
3CompletedTreatmentHigh HbA1c Level / Inadequate Glycaemic Control / Type 2 Diabetes Mellitus1
3CompletedTreatmentInadequate Glycaemic Control / Type 2 Diabetes Mellitus / Type2 Diabetes Mellitus1
3CompletedTreatmentType 2 Diabetes Mellitus25
3Not Yet RecruitingTreatmentCVD / Myocardial Infarction / Pre-Diabetic / Type 2 Diabetes Mellitus1
3Not Yet RecruitingTreatmentType 2 Diabetes Mellitus2
3RecruitingTreatmentBMI >30 kg/m2 / Polycystic Ovaries Syndrome1
3RecruitingTreatmentBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
3RecruitingTreatmentChronic Kidney Disease (CKD)1
3RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
3RecruitingTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF)1
3RecruitingTreatmentType 2 Diabetes Mellitus4
3SuspendedTreatmentType 2 Diabetes Mellitus1
4Active Not RecruitingTreatmentLeft Ventricular Hypertrophy / Type 2 Diabetes Mellitus1
4Active Not RecruitingTreatmentPre-Diabetic / Prehypertension1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus3
4CompletedBasic ScienceHigh Cholesterol / Type 2 Diabetes Mellitus1
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedTreatmentBlood Pressures / BMI >30 kg/m2 / Cardiac Hypertrophy / High Blood Pressure (Hypertension) / Microalbuminuria / Type 2 Diabetes Mellitus / Vascular Stiffness1
4CompletedTreatmentDiabetes Mellitus (DM)1
4CompletedTreatmentDiabetes Mellitus (DM) / Heart Failure, Unspecified1
4CompletedTreatmentGlomerulosclerosis, Focal Segmental1
4CompletedTreatmentHyperglycemia Steroid-induced1
4CompletedTreatmentImpaired Fasting Glucose (IFG) / Impaired Glucose Tolerance (IGT) / Pre-Diabetic1
4CompletedTreatmentInadequate Glycaemic Control / Type 2 Diabetes Mellitus / Type2 Diabetes Mellitus1
4CompletedTreatmentIschaemic Heart Diseases / Type 2 Diabetes Mellitus1
4CompletedTreatmentMetabolic Syndromes1
4CompletedTreatmentType 2 Diabetes Mellitus7
4Enrolling by InvitationTreatmentHigh Blood Pressure (Hypertension)1
4Not Yet RecruitingNot AvailableDiabetes Mellitus (DM) / Hypoglycemic Episodes1
4Not Yet RecruitingTreatmentCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentCarotid Artery Diseases / Coronary Artery Disease / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentCoronary Disease With Diabetes Mellitus1
4Not Yet RecruitingTreatmentEvaluate Ketogenic Stress1
4Not Yet RecruitingTreatmentOral Antidiabetics / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentType 2 Diabetes Mellitus4
4RecruitingBasic ScienceHepatic Glucose Metabolism1
4RecruitingBasic ScienceSkeletal Muscle Insulin Sensitivity / Type 2 Diabetes Mellitus1
4RecruitingBasic ScienceType 2 Diabetes Mellitus3
4RecruitingPreventionDiabetic Nephropathies / Type 2 Diabetes Mellitus1
4RecruitingTreatmentBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
4RecruitingTreatmentCardiovascular Disease (CVD) / Type2 Diabetes1
4RecruitingTreatmentChronic Heart Failure With Preserved Systolic Function1
4RecruitingTreatmentChronic Heart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentDiabetes Mellitus (DM)2
4RecruitingTreatmentEndothelial Function / Type 2 Diabetes Mellitus1
4RecruitingTreatmentFasting Glucose / Glucose Excursion / Glycemic Control1
4RecruitingTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4RecruitingTreatmentKidney Function Tests / Type 2 Diabetes Mellitus1
4RecruitingTreatmentSteatosis, Liver / Type2 Diabetes1
4RecruitingTreatmentType 2 Diabetes Mellitus12
4Unknown StatusTreatmentType 2 Diabetes Mellitus1
4WithdrawnTreatmentType 2 Diabetes Mellitus2
Not AvailableActive Not RecruitingBasic ScienceInsulin Sensitivity / Multiple Mitochondrial Dysfunctions Syndrome1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus2
Not AvailableCompletedBasic ScienceType 2 Diabetes Mellitus1
Not AvailableNot Yet RecruitingNot AvailableType 2 Diabetes Mellitus1
Not AvailableRecruitingOtherType 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentImpaired Fasting Glucose (IFG) / Impaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentType 2 Diabetes Mellitus1
Not AvailableTerminatedNot AvailableType 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral10 mg
Tablet, film coatedOral5 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
TabletOral10 mg
TabletOral5 mg
TabletOral
Tablet, film coatedOral
Tablet, film coated, extended releaseOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8216180No2008-01-122028-01-12Us
US8439864No2008-03-252028-03-25Us
US6667061Yes2000-11-252020-11-25Us
US6495164No2000-05-252020-05-25Us
US6872700No2000-01-142020-01-14Us
US6956026No1998-01-072018-01-07Us
US7741269No1998-01-072018-01-07Us
US9238076No2004-04-152024-04-15Us
US8906851No2006-08-182026-08-18Us
US7612176No2005-04-132025-04-13Us
US8431685No2005-04-132025-04-13Us
US8461105No2005-04-132025-04-13Us
US8329648No2006-08-182026-08-18Us
US7456254No2005-06-302025-06-30Us
US7563871No2004-04-152024-04-15Us
US6824822No2002-10-092022-10-09Us
US6479065No2000-08-102020-08-10Us
US7223440No2001-08-312021-08-31Us
USRE44186No2003-07-312023-07-31Us
US8628799No2005-07-132025-07-13Us
US8685934No2010-05-262030-05-26Us
US8501698No2007-06-202027-06-20Us
US6414126No2000-10-042020-10-04Us
US6515117No2000-10-042020-10-04Us
US6936590No2000-10-042020-10-04Us
US9198925No2000-10-042020-10-04Us
US7919598No2009-12-162029-12-16Us
US8361972No2008-03-212028-03-21Us
US8716251No2008-03-212028-03-21Us
US7851502No2008-08-192028-08-19Us
US8221786No2008-03-212028-03-21Us
US9616028No2010-11-122030-11-12Us
US9320853No2008-03-252028-03-25Us
US8827963No2009-02-042029-02-04Us
US8712615No2010-01-182030-01-18Us
US8998876No2010-01-072030-01-07Us
US8758292No2007-11-122027-11-12Us
US8690837No2009-05-192029-05-19Us
US8721615No2010-01-182030-01-18Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.173 mg/mLALOGPS
logP2.52ALOGPS
logP2.11ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)12.57ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area99.38 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity104.93 m3·mol-1ChemAxon
Polarizability42.36 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

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
Diphenylmethanes / Hexoses / C-glycosyl compounds / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Chlorobenzenes / Aryl chlorides / Oxanes / Secondary alcohols
show 6 more
Substituents
Phenolic glycoside / Diphenylmethane / Hexose monosaccharide / C-glycosyl compound / Phenoxy compound / Phenol ether / Alkyl aryl ether / Chlorobenzene / Halobenzene / Aryl chloride
show 17 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, organochlorine compound, C-glycosyl compound (CHEBI:85078)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Obermeier M, Yao M, Khanna A, Koplowitz B, Zhu M, Li W, Komoroski B, Kasichayanula S, Discenza L, Washburn W, Meng W, Ellsworth BA, Whaley JM, Humphreys WG: In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010 Mar;38(3):405-14. doi: 10.1124/dmd.109.029165. Epub 2009 Dec 8. [PubMed:19996149]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Forxiga Assessment report [File]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [PubMed:24105299]

Drug created on March 19, 2008 10:22 / Updated on October 21, 2018 20:33