Ferroptosis-centered Drug Response Information
General Information of the Drug (ID: ferrodrug0089)
Name |
Zoledronic acid
|
||||
---|---|---|---|---|---|
Synonyms |
Zoledronic acid; 118072-93-8; Zoledronate; Zometa; Reclast; Aclasta; (1-Hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl)diphosphonic acid; CGP 42446; (1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid; Zoledronic Acid Anhydrous; C5H10N2O7P2; Anhydrous Zoledronic Acid; (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid; Phosphonic acid, [1-hydroxy-2-(1H-imidazol-1-yl)ethylidene]bis-; ZOL; Zoledronic-d3 Acid; Orazol; ZOL 446; [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid); Zoledronic acid (INN); CGP-42446; Reclast (TN); Zometa (TN); CHEMBL924; Zoledronic Acid Teva; Zoledronic Acid, Anhydrous; NSC-721517; Zoledronic Acid Medac; 2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid; DTXSID0042668; CHEBI:46557; [1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid; 70HZ18PH24; NCGC00159521-02; (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid; CGP-42446A; Zoledronate hydrate; Zoledronic acid [USAN:INN:BAN]; Phosphonic acid, (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bis-; Zoladrona acid mylan; ZOLEDRONIC; Zoledronic acid accord; ZOLEDRONIC ACID [INN]; Zomera; 1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid; Bisphosphonate 3; Zometa (Novartis); Aclasta and Reclast; [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bisphosphonic acid; zoledronic-acid; UNII-70HZ18PH24; BPH 91; (1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl)bis(phosphonic acid); [1-HYDROXY-2-(1H-IMIDAZOL-1-YL)-ETHYLIDENE]BISPHOSPHONIC ACID; Zoledronic acid, Zoledronate; BIDD:PXR0134; SCHEMBL19054; ZOLEDRONIC ACID [MI]; BIDD:GT0292; Zoledronic Acid (Zoledronate); GTPL3177; JMC515594 Compound 55; DTXCID8022668; BDBM12578; CGP42446A; ZOLEDRONIC ACID [WHO-DD]; XRASPMIURGNCCH-UHFFFAOYSA-N; HMS2089O09; BCP22750; CGP-4244; Tox21_111739; HB0674; MFCD00867791; NSC721517; s1314; STL452893; AKOS005145739; AB07564; AC-1092; CS-1829; DB00399; HS-0091; NSC 721517; NCGC00159521-03; NCGC00159521-04; NCGC00159521-05; NCGC00159521-09; NCGC00159521-18; HY-13777; CAS-118072-93-8; FT-0601384; Z0031; D08689; EN300-117269; H11422; S00092; AB01273947-01; AB01273947-02; AB01273947-03; AB01273947_04; A803876; Q218507; SR-05000001436; Q-201946; SR-05000001436-1; 1-Hydroxy-2-(1-imidazolyl)ethane-1,1-diphosphonic Acid; Z1501485360; (1-Hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl)diphosphonicacid
Click to Show/Hide
|
||||
Structure |
![]() |
||||
Formula |
C5H10N2O7P2
|
||||
IUPAC Name |
(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid
|
||||
Canonical SMILES |
C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O
|
||||
InChI |
InChI=1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)
|
||||
InChIKey |
XRASPMIURGNCCH-UHFFFAOYSA-N
|
||||
PubChem CID |
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 3 item(s) under this Target | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target | [1] | ||||
Responsed Disease | Osteosarcoma | ICD-11: 2B51 | |||
Responsed Regulator | NADPH--cytochrome P450 reductase (POR) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | MG-63 cells | Osteosarcoma | Homo sapiens | CVCL_0426 | |
143B cells | Osteosarcoma | Homo sapiens | CVCL_2270 | ||
In Vivo Model |
All animal experimentation was approved by the Ethics Committee of The Eighth Affiliated Hospital of Sun Yat-sen University. Each group consisted of five female BALB/c nude 4-week-old mice, and the studies were run twice. 143B cells were treated with ZOL or DMEM containing 10% FBS for 2 days. Two sets of BALB/c nude mice were used in the study (ZOL group and NC group). The ZOL group and NC group were subcutaneously injected with ZOL-treated 143B cells or normal 143B cells, respectively, to form xenograft tumors. After 2 weeks, we subcutaneously injected 100 ul ZOL (100 ug/kg) into the experimental group and 100 ul saline into the NC group twice a week. Then, after 4 weeks, mice from both groups were humanely killed, the tumor diameter was measured, and the tumor tissue was stained with HE.
Click to Show/Hide
|
||||
Response regulation | Zoledronic acid (ZOL) induces ferroptosis by upregulating POR expression to increase ROS levels and upregulate lipid peroxidation levels in osteosarcoma cells. POR may be used as a therapeutic target to inhibit osteosarcoma. | ||||
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target | [2] | ||||
Responsed Disease | Osteonecrosis | ICD-11: FB81 | |||
Responsed Regulator | F-box only protein 9 (FBXO9) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | RAW 264.7 cells | Leukemia | Mus musculus | CVCL_0493 | |
Response regulation | FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9 -mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ). | ||||
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target | [2] | ||||
Responsed Disease | Osteonecrosis | ICD-11: FB81 | |||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | RAW 264.7 cells | Leukemia | Mus musculus | CVCL_0493 | |
Response regulation | FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ). | ||||
Prostaglandin G/H synthase 2 (PTGS2)
In total 1 item(s) under this Target | ||||
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target | [3] | |||
Target for Ferroptosis | Marker | |||
Responsed Disease | Osteosarcoma | ICD-11: 2B51 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Cell Process | Cell ferroptosis | |||
In Vitro Model | HEK-293T cells | Normal | Homo sapiens | CVCL_0063 |
MG-63 cells | Osteosarcoma | Homo sapiens | CVCL_0426 | |
U2OS cells | Osteosarcoma | Homo sapiens | CVCL_0042 | |
MNNG/HOS Cl #5 cells | Osteosarcoma | Homo sapiens | CVCL_0439 | |
Response regulation | Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. | |||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this Target | ||||
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target | [3] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Osteosarcoma | ICD-11: 2B51 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Cell Process | Cell ferroptosis | |||
In Vitro Model | HEK-293T cells | Normal | Homo sapiens | CVCL_0063 |
MG-63 cells | Osteosarcoma | Homo sapiens | CVCL_0426 | |
U2OS cells | Osteosarcoma | Homo sapiens | CVCL_0042 | |
MNNG/HOS Cl #5 cells | Osteosarcoma | Homo sapiens | CVCL_0439 | |
Response regulation | Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. | |||
References