dapagliflozin   Click here for help

GtoPdb Ligand ID: 4594

Synonyms: BMS-512148 | Farxiga® | Forxiga®
Approved drug PDB Ligand
dapagliflozin is an approved drug (EMA (2012), FDA (2014))
Compound class: Synthetic organic
Comment: Dapagliflozin is a derivative of naturally occurring dihydrocholine glucoside. It acts as a sodium-glucose cotransporter 2 (SGLT-2) inhibitor. In addition to clinical efficacy in type 2 diabetes, evidence from clinical trial suggests that dapagliflozin is of benefit in treating heart failure with or without type 2 diabetes as a comorbidity [7].

SARS-CoV-2 and COVID-19: Based on the cardio- and renoprotective benefits of dapagliflozin in T2DM patients, it was evaluated vs. placebo in 1250 hospitalised COVID-19 patients (NCT04350593) [4], to determine if it would provide similar protection from organ damage caused by SARS-CoV-2 infection. The drug treatment effected a non-significant reduction in the risk of organ failure or death [5]. Subsequent to this finding, another approved SGLT2 inhibitor empagliflozin was added to the RECOVERY trial.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View more information in the IUPHAR Pharmacology Education Project: dapagliflozin

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 4
Rotatable bonds 6
Topological polar surface area 99.38
Molecular weight 408.13
XLogP 2.94
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCOc1ccc(cc1)Cc1cc(ccc1Cl)C1OC(CO)C(C(C1O)O)O
Isomeric SMILES CCOc1ccc(cc1)Cc1cc(ccc1Cl)[C@@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O
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
InChI Key JVHXJTBJCFBINQ-ADAARDCZSA-N
No information available.
Summary of Clinical Use Click here for help
Approved to treat diabetes mellitus, type 2.
The fixed-dose drug Xigduo XR® contains dapagliflozin (as dapagliflozin propanediol monohydrate PubChem CID 56841155) and metformin hydrochloride.
Results have been published for trial NCT03036124 and these conclude that dapagliflozin reduced worsening heart failure or death from cardiovascular causes irrespective of diabetes status, in patients with heart failure and a reduced ejection fraction [7]. Clinical trial NCT03619213 is evaluating whether this efficacy is retained in patients with heart failure and preserved ejection fraction.
In July 2021, the FDA approved dapagliflozin as a therapy for chronic kidney disease [1-2], based on evidence from the DAPA-CKD trial (NCT03036150) [8].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Dapagliflozin inhibits sodium-glucose transport protein subtype 2 (SGLT2), which accounts for >90% of glucose reabsorption from the kidneys. Inhibition of this transporter leads to excretion of blood glucose into urine. Dapagliflozin is >1000 times more inhibitory at SGLT2 than SGLT1, meaning that its effects on intestinal glucose absorption are negligible. Although this drug could be equally effective in treating type 1 diabetes, its approval restricts use to type 2 disease.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03036124 Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure Phase 3 Interventional AstraZeneca
NCT03619213 Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. Phase 3 Interventional AstraZeneca
NCT04350593 Dapagliflozin in Respiratory Failure in Patients With COVID-19 Phase 3 Interventional Saint Luke's Health System 5
NCT03036150 A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease Phase 3 Interventional AstraZeneca 8
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)