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

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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
68740
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.

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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
Ref 1 Zoledronic acid induces ferroptosis by upregulating POR in osteosarcoma. Med Oncol. 2023 Apr 10;40(5):141. doi: 10.1007/s12032-023-01988-w.
Ref 2 Zoledronic acid promotes osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation. PeerJ. 2021 Dec 16;9:e12510. doi: 10.7717/peerj.12510. eCollection 2021.
Ref 3 Zoledronic acid induces ferroptosis by reducing ubiquinone and promoting HMOX1 expression in osteosarcoma cells. Front Pharmacol. 2023 Jan 4;13:1071946. doi: 10.3389/fphar.2022.1071946. eCollection 2022.