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 interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

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
References
1. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P et al.. (2020)
Dapagliflozin in Patients with Chronic Kidney Disease.
N Engl J Med, 383 (15): 1436-1446. [PMID:32970396]
2. Jafar TH. (2021)
FDA approval of dapagliflozin for chronic kidney disease: a remarkable achievement?.
Lancet, 398 (10297): 283-284. [PMID:34097853]
3. Kang SY, Song KS, Lee J, Lee SH, Lee J. (2010)
Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors.
Bioorg Med Chem, 18 (16): 6069-79. [PMID:20637636]
4. Kosiborod M, Berwanger O, Koch GG, Martinez F, Mukhtar O, Verma S, Chopra V, Javaheri A, Ambery P, Gasparyan SB et al.. (2021)
Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study.
Diabetes Obes Metab, 23 (4): 886-896. [PMID:33319454]
5. Kosiborod MN, Esterline R, Furtado RHM, Oscarsson J, Gasparyan SB, Koch GG, Martinez F, Mukhtar O, Verma S, Chopra V et al.. (2021)
Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Diabetes Endocrinol, 9 (9): 586-594. [PMID:34302745]
6. Li AR, Zhang J, Greenberg J, Lee T, Liu J. (2011)
Discovery of non-glucoside SGLT2 inhibitors.
Bioorg Med Chem Lett, 21 (8): 2472-5. [PMID:21398124]
7. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J et al.. (2019)
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.
N Engl J Med, 381 (21): 1995-2008. [PMID:31535829]
8. Wheeler DC, Stefánsson BV, Jongs N, Chertow GM, Greene T, Hou FF, McMurray JJV, Correa-Rotter R, Rossing P, Toto RD et al.. (2021)
Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial.
Lancet Diabetes Endocrinol, 9 (1): 22-31. [PMID:33338413]