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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2D Structure
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Physico-chemical Properties
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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
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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
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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
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