General Information of the Drug (ID: ferrodrug0171)
Name
Empagliflozin
Synonyms
Empagliflozin; 864070-44-0; JARDIANCE; BI 10773; BI10773; BI-10773; Empagliflozin (BI 10773); UNII-HDC1R2M35U; HDC1R2M35U; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(((S)-tetrahydrofuran-3-yl)oxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; CHEBI:82720; 1-chloro-4-(glucopyranos-1-yl)-2-(4-(tetrahydrofuran-3-yloxy)benzyl)benzene; (2S,3R,4R,5S,6R)-2-[4-chloro-3-({4-[(3S)-oxolan-3-yloxy]phenyl}methyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol; (1S)-1,5-anhydro-1-(4-chloro-3-{4-[(3S)-tetrahydrofuran-3-yloxy]benzyl}phenyl)-D-glucitol; GLYXAMBI COMPONENT EMPAGLIFLOZIN; EMPAGLIFLOZIN COMPONENT OF GLYXAMBI; EMPAGLIFLOZIN COMPONENT OF SYNJARDY; TRIJARDY XR COMPONENT EMPAGLIFLOZIN; EMPAGLIFLOZIN COMPONENT OF TRIJARDY XR; (2S,3R,4R,5S,6R)-2-[4-CHLORO-3-[[4-[(3S)-OXOLAN-3-YL]OXYPHENYL]METHYL]PHENYL]-6-(HYDROXYMETHYL)OXANE-3,4,5-TRIOL; D-Glucitol, 1,5-anhydro-1-C-(4-chloro-3-((4-(((3S)-tetrahydro-3-furanyl)oxy)phenyl)methyl)phenyl)-, (1S)-; Empagliflozin (BI-10773;BI 10773;BI10773); (1S)-1,5-ANHYDRO-1-C-(4-CHLORO-3-((4-(((3S)-OXAN-3-YL)OXY)PHENYL)METHYL)PHENYL)-D-GLUCITOL; (1S)-1,5-anhydro-1-C-{4-chloro-3-((4-{((3S)-oxolan-3-yl)oxy}phenyl)methyl)phenyl}-D-glucitol; (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol; Empagliflozin [INN]; Empagliflozin [USAN:INN]; Empagliflozina; Empagliflozine; Empagliflozinum; C23H27ClO7; MFCD22566222; Jardiance (TN); (1S)-1,5-anhydro-1-(4-chloro-3-(4-((3S)-tetrahydrofuran-3-yloxy)benzyl)phenyl)-D-glucitol; (1S)-1,5-Anhydro-1-C-(4-chloro-3-((4-(((3S)-oxolan-3-yl)oxy)phenyl)methyl)phenyl)-D-glucitol; 7R3; EMPAGLIFLOZIN [MI]; BI-10773;Empagliflozin; EMPAGLIFLOZIN [JAN]; EMPAGLIFLOZIN [USAN]; Empagliflozin (BI10773); EMPAGLIFLOZIN [VANDF]; SCHEMBL899986; EMPAGLIFLOZIN [WHO-DD]; GTPL4754; CHEMBL2107830; Empagliflozin (JAN/USAN/INN); A10BK03; AMY1858; EX-A414; BDBM150162; DTXSID601026093; EMPAGLIFLOZIN [ORANGE BOOK]; BBL104150; HB4638; s8022; STL557964; US8980829, EMPAGLIFLOZIN; AKOS024464680; CCG-269242; CS-0940; DB09038; DS-9824; PB23119; (1S)-1,5-Anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-D-glucitol; AC-27643; HY-15409; SW219120-1; C22194; D10459; EN300-7422890; A852380; AU-004/43508285; Q5373824; Z2235802079; 1,5-anhydro-1-{4-chloro-3-[4-(tetrahydro-3-furanyloxy)benzyl]phenyl}hexitol; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-((S)-tetrahydrofuran-3-yloxy)benzyl)phenyl)-6-(hydroxyMethyl)-tetrahydro-2H-pyran-3,4,5-triol; (2S,3R,4R,5S,6R)-2-(4-Chloro-3-(4-((S)-tetrahydrofuran-3-yloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (2S,3R,4R,5S,6R)-2-[4-Chloro-3-[[4-[(3S)-tetrahydrofuran-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol; D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-, (1S)-; (1S)-1,5-Anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-D-glucitol; BI 10773; Empagliflozin; Jardiance

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Status
Approved
Drug Type
Small molecular drug
Structure
Formula
C23H27ClO7
IUPAC Name
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
Canonical SMILES
C1COCC1OC2=CC=C(C=C2)CC3=C(C=CC(=C3)C4C(C(C(C(O4)CO)O)O)O)Cl
InChI
InChI=1S/C23H27ClO7/c24-18-6-3-14(23-22(28)21(27)20(26)19(11-25)31-23)10-15(18)9-13-1-4-16(5-2-13)30-17-7-8-29-12-17/h1-6,10,17,19-23,25-28H,7-9,11-12H2/t17-,19+,20+,21-,22+,23-/m0/s1
InChIKey
OBWASQILIWPZMG-QZMOQZSNSA-N
PubChem CID
11949646
TTD Drug ID
D06ALD
Full List of Ferroptosis Target Related to This Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Liver fibrosis ICD-11: DB93
Responsed Regulator Sestrin-2 (SESN2) Suppressor
Pathway Response Autophagy hsa04140
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model hLCs (Liver cells)
In Vivo Model
After a one-week acclimatization period, rats were randomly divided into four experimental groups of six rats each. Group I (the control group) received saline intraperitoneally in the same manner as BLM injections, as well as 1% carboxymethyl cellulose (CMC) orally in the same manner as EMPA. Group II (the BLM-treated group) received BLM (15 mg/kg) intraperitoneally three times per week for four successive weeks in order to induce pulmonary fibrosis. Group III (the EMPA-treated group) received EMPA dissolved in 1% CMC orally via oral gavage at a dose of 10 mg/kg/day throughout the experimental period. Group IV (the combined EMPA and BLM-treated group) received EMPA (10 mg/kg) orally via oral gavage seven days before BLM administration and continued for four weeks after BLM injection.

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Response regulation Empagliflozin has a promising protective effect against BLM-induced liver fibrosis in rats by enhancing autophagy and mitigating ferroptosis, inflammation, and ER stress via modulating the Sesn2/AMPK/Nrf2/HO-1 signaling pathway.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Diabetes mellitus ICD-11: 5A10
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model C2C12 cells Normal Mus musculus CVCL_0188
HUVECs (Human umbilical vein endothelial cells)
MOVAS-1 cells Normal Homo sapiens CVCL_0F08
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
For diabetes induction, C57BL/6 mice were fed with high fat diet (HFD) for 3 weeks (20% kcal protein, 20% kcal carbohydrate, and 60% kcal fat). Intraperitoneal administration of 60 mg/kg body weight streptozotocin (STZ, Sigma-Aldrich, St Louis, MO, USA) diluted in sodium citrate buffer was then performed for the following six days. Mice were fasted overnight prior to each STZ injection and blood glucose level measurement. Blood glucose level was evaluated using Accu-Check Integra (Roche Diagnostics, Shanghai, China). Mice with blood glucose level above 16.6 mM were assumed as diabetic mice, and were used for establishing diabetic HLI model as described previously.

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Response regulation Empagliflozin, a clinical hypoglycemic gliflozin drug, can inhibit ferroptosis and enhance skeletal muscle cell survival and paracrine function under hyperglycemic condition via restoring the expression of GPX4. This study highlights the potential of intramuscular injection of empagliflozin for treating diabetic hindlimb ischemia.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Responsed Disease Cardiomyopathy ICD-11: BC43
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model AT-1 cells Normal Mus musculus CVCL_JK52
In Vivo Model
All animal procedures were approved by the Animal Care and Use Committees at the Second Affiliated Hospital of Nanchang University (Nanchang, China) and Zhongshan Hospital Fudan University (Shanghai, China). In brief, adult male C57BL/6J mice were intraperitoneally delivered TZM at a dose of 10 mg/kg once per week for 6 weeks. A cohort of mice received Empagliflozin at a dose of 10 mg/kg twice per week for 6 weeks. All mice were maintained on a 12/12-light/dark cycle with free access to tap water and lab chow until experimentation. Blood glucose and serum triglyceride levels were obtained using a commercial glucometer and ELISA commercial kits, respectively. Serum levels oflactic dehydrogenase(LDH) and troponin I were measured using chemiluminescent immunoassays. To discern the involvement of ferroptosis in TZM-induced cardiotoxicity, a cohort of TZM challenged C57BL/6J mice (10 mg/kg once per week for 4 weeks) also received the ferroptosis inhibitor liproxtatin-1 (LIP-1, 10 mg/kg, i.p., every other day) during the entire duration of TZM challenge.

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Response regulation SGLT2 inhibitor empagliflozin may be considered in TZM-elicited cardiotoxicity (including cardiac remodeling and contractile dysfunction, DNA damage, oxidative stress and cell death).
References
Ref 1 Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy. Int J Mol Sci. 2023 May 30;24(11):9481. doi: 10.3390/ijms24119481.
Ref 2 SGLT2 inhibitor empagliflozin promotes revascularization in diabetic mouse hindlimb ischemia by inhibiting ferroptosis. Acta Pharmacol Sin. 2023 Jun;44(6):1161-1174. doi: 10.1038/s41401-022-01031-0. Epub 2022 Dec 12.
Ref 3 Empagliflozin attenuates trastuzumab-induced cardiotoxicity through suppression of DNA damage and ferroptosis. Life Sci. 2023 Jan 1;312:121207. doi: 10.1016/j.lfs.2022.121207. Epub 2022 Nov 17.