Ferroptosis-centered Drug Response Information
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
Click to Show/Hide
|
||||
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 | |||||
TTD Drug ID |
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.
Click to Show/Hide
|
||||
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.
Click to Show/Hide
|
||||
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.
Click to Show/Hide
|
||||
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