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
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]