Zoledronate (CED0002047)

Record Information
Version1.0
Creation Date2009-07-15 20:44:41 UTC
Update Date2026-05-14 16:37:35 UTC
Accession NumberCHEM002114
Identification
Common NameZoledronate
ClassSmall Molecule
Description
Zoledronate belongs to the bisphosphonates, a subclass of organic phosphonic acids and derivatives within the organic compounds. It is an exogenous solid with the formula C5H10N2O7P2 and an average molecular weight of 272.09 g/mol. This compound is used as a drug (PMC10692760) and a bone density conservation agent (PMC10692760), specifically within healthcare, pharmaceuticals, and veterinary products for the treatment of bone diseases. It is administered via intravenous exposure. Zoledronate targets farnesyl pyrophosphate synthase (FDPS), geranylgeranyl pyrophosphate synthase (GGPS1), and matrix metalloproteinase-14 (MMP14). Its action on bone tissue is partly based on its affinity for hydroxyapatite in the bone mineral matrix. As a nitrogen-containing bisphosphonate, it acts as an analogue of isoprenoid diphosphate lipids to inhibit FPP synthase in the mevalonate pathway, which prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) in osteoclasts. Therapeutically, zoledronate is used to treat osteoporosis (PMC10560398, PMC12051078, PMC12068388, PMC12896522, PMC2971711, PMC4307702), hypercalcemia (PMC10547673, PMC12061736), multiple myeloma (PMC1779467, PMC3699134, PMC8951013), breast cancer (PMC1779467), prostate cancer (PMC1779467), lung cancer (PMC1779467), cancer (PMC3688704), and renal cell carcinoma (PMC11029699). It has demonstrated therapeutic effects on colorectal cancer (PMC5384426), arrhythmia (PMC12409151), pain (PMC5037694, PMC9645513), multiple myeloma (PMC3722725, PMC5740853), and breast cancer (PMC3480876, PMC4293349, PMC4723356). Reported adverse effects associated with the compound include fever (PMC2971711, PMC8533546) and acute renal failure (PMC13228822).
Contaminant Type
  • Antihypocalcemic Agent
  • Antiresorptive
  • Bisphosphonate
  • Bone Density Conservation Agent
  • Drug
  • Human Neurotoxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acidChEBI
(1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acidChEBI
ReclastChEBI
ZOLChEBI
ZometaKegg
(1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonateGenerator
(1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonateGenerator
Zoledronic acidGenerator
2-(Imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acidHMDB
Novartis brand OF zoledronic acidHMDB
Zoledronic acid anhydrousHMDB
Chemical FormulaC5H10N2O7P2
Average Molecular Mass272.090 g/mol
Monoisotopic Mass271.996 g/mol
CAS Registry Number118072-93-8
IUPAC Name[1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid
Traditional Namezoledronate
SMILESOC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O
InChI IdentifierInChI=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)
InChI KeyXRASPMIURGNCCH-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • N-substituted imidazole
  • Heteroaromatic compound
  • Organophosphonic acid
  • Imidazole
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organophosphorus compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Applications
Biological Roles
Chemical RolesNot Available
Organoleptic EffectsNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilitySparingly soluble
Predicted Properties
PropertyValueSource
Water Solubility3.27 g/LALOGPS
logP-0.93ALOGPS
logP-3.9ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)0.66ChemAxon
pKa (Strongest Basic)6.67ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area153.11 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity52.16 m³·mol⁻¹ChemAxon
Polarizability20.1 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrumsplash10-001i-9120000000-239c3921d9c0513b29bfNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS Spectrumsplash10-0089-9010000000-350e054fb0333ac6c489Not AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-000i-0910000000-6c7cee1b60ea3968e2f7Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-0190000000-d743d302781bf9a387dcNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-001l-8910000000-89833833ce5df6ce7fbfNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-014i-9350000000-6a8817aebcf8b58c9872Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-1290000000-3a385a1ab40b3030223aNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0fki-4690000000-90b5d47e0913184a3303Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-004i-9100000000-8fed5642f16554892c2dNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00dl-0690000000-d8e121c2f8fde6d36c50Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-1490000000-73b24204457ff8cb45cbNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00lr-9100000000-a6b7ed66230e1c22c0cfNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0fk9-0090000000-39599d85059cab3fb733Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0iu0-9220000000-54fc3ff7d337e2817e04Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-03mi-9110000000-c37cf2658c6d4e001274Not AvailableView Spectrum
1D NMR1H NMR Spectrum (1D, D2O, predicted)Not AvailableNot AvailableView Spectrum
1D NMR13C NMR Spectrum (1D, D2O, predicted)Not AvailableNot AvailableView Spectrum
Toxicity Profile
Mechanism of ToxicityThe action of zoledronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Zoledronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates such as zoledronate appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelNot Available
SymptomsThere is no experience of acute overdose. Two patients received zoledronate (32 mg) over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant hypocalcemia, hypophosphatemia, and hypomagnesemia.
TreatmentNot Available
Toxicity Values
Toxicity ValueUnitValue RangeOrganismDose DescriptorRoute of ExposurePredicted or ExperimentalReference
2027.0Log mg/kg[1100:3600]RatLD50oralpredictedNot Available
Health Effects
Health EffectRelationshipDirectionReference
lung canceris_treatment_forNot AvailablePMC1779467
canceris_treatment_forNot AvailablePMC3688704
breast cancerhas_therapeutic_effect_onNot AvailablePMC3480876 , PMC4293349 , PMC4723356
breast canceris_treatment_forNot AvailablePMC1779467
colorectal cancerhas_therapeutic_effect_onNot AvailablePMC5384426
osteoporosisis_treatment_forNot AvailablePMC10560398 , PMC10560398 , PMC12051078 , PMC12068388 , PMC12896522 , PMC2971711 , PMC2971711 , PMC2971711 , PMC2971711 , PMC4307702
multiple myelomahas_therapeutic_effect_onNot AvailablePMC3722725 , PMC5740853
multiple myelomais_treatment_forNot AvailablePMC1779467 , PMC3699134 , PMC8951013
feverassociated_withNot AvailablePMC2971711 , PMC8533546
painhas_therapeutic_effect_onNot AvailablePMC5037694 , PMC9645513
Prostate canceris_treatment_forNot AvailablePMC1779467
hypercalcemiais_treatment_forNot AvailablePMC10547673 , PMC12061736
renal cell carcinomais_treatment_forNot AvailablePMC11029699
acute renal failureassociated_withNot AvailablePMC13228822
arrhythmiahas_therapeutic_effect_onNot AvailablePMC12409151
osteonecrosisassociated_withNot AvailablePMC12025247
juvenile myelomonocytic leukemiais_treatment_forNot AvailablePMC9138592
breast carcinomais_treatment_forNot AvailablePMC1779467
fibrous dysplasiahas_therapeutic_effect_onNot AvailablePMC5682380
Exposure Sources
Source IDSourceSectorReference
367Drugs for treatment of bone diseasesHealthcare, pharmaceuticals & veterinary productsNot Available
525Line Transmission SystemsElectrical & Electronic EquipmentNot Available
537Television SystemsElectrical & Electronic EquipmentNot Available
556Cigar CigarettesHousehold cleaning & consumer productsNot Available
559Non Electric Simulated Smoking DevicesHousehold cleaning & consumer productsNot Available
560Other Smoking RequisitesHousehold cleaning & consumer productsNot Available
630ToysRecreation & sports surfacesNot Available
650Purses Luggage Hand BagsTextiles, leather & furnishingsNot Available
Pathways
4 pathways
Zoledronate Pathway
Zoledronate Pathway
Zoledronate Action Pathway
Zoledronate Action Pathway
Zoledronate Action Pathway
Zoledronate Action Pathway
Zoledronate Drug Metabolism Pathway
Zoledronate Drug Metabolism Pathway
Targets
StructureProteinUniProt IDOrganismRelationshipDetails
Farnesyl pyrophosphate synthase structureClick to view 3D structureFarnesyl pyrophosphate synthaseP14324HumansPredicted (SEA)0.544945
Butyrophilin subfamily 3 member A1 structureClick to view 3D structureButyrophilin subfamily 3 member A1O00481HumansPredicted (SEA)0.0778492
Click to view 3D structureFarnesyl pyrophosphate synthaseQ0GKD7Leishmania donovaniPredicted (SEA)0.700643
Geranylgeranyl pyrophosphate synthase structureClick to view 3D structureGeranylgeranyl pyrophosphate synthaseO95749HumansPredicted (SEA)0.700643
Click to view 3D structureGeranylgeranyl pyrophosphate synthase BTS1Q12051Saccharomyces cerevisiae S288cPredicted (SEA)0.155698
Farnesyl diphosphate synthase structureClick to view 3D structureFarnesyl diphosphate synthaseP22939Escherichia coli (strain K12)Predicted (SEA)0.0778492
Click to view 3D structureFarnesyl pyrophosphate synthaseQ4QBL1Leishmania majorPredicted (SEA)0.233548
Camphor 5-monooxygenase structureClick to view 3D structureCamphor 5-monooxygenaseP00183Pseudomonas putidaPredicted (SEA)0.233548
Cytochrome P450 11B1, mitochondrial structureClick to view 3D structureCytochrome P450 11B1, mitochondrialP15538HumansPredicted (SEA)16.504
Cytochrome P450 11B2, mitochondrial structureClick to view 3D structureCytochrome P450 11B2, mitochondrialP19099HumansPredicted (SEA)15.8812
Click to view 3D structureSteroid 17-alpha-hydroxylase/17,20 lyaseP11715Rattus norvegicusPredicted (SEA)8.32987
Aromatase structureClick to view 3D structureAromataseP11511HumansPredicted (SEA)49.5121
Carbonic anhydrase 9 structureClick to view 3D structureCarbonic anhydrase 9Q16790HumansPredicted (SEA)238.53
Carbonic anhydrase 1 structureClick to view 3D structureCarbonic anhydrase 1P00915HumansPredicted (SEA)260.094
72 kDa type IV collagenase structureClick to view 3D structure72 kDa type IV collagenaseP08253HumansPredicted (SEA)313.81
Carbonic anhydrase 2 structureClick to view 3D structureCarbonic anhydrase 2P00918HumansPredicted (SEA)317.08
Carbonic anhydrase 12 structureClick to view 3D structureCarbonic anhydrase 12O43570HumansPredicted (SEA)216.499
Carbonic anhydrase 14 structureClick to view 3D structureCarbonic anhydrase 14Q9ULX7HumansPredicted (SEA)127.283
Click to view 3D structureHeme oxygenase 1P06762Rattus norvegicusPredicted (SEA)6.22794
Cytochrome P450 2D6 structureClick to view 3D structureCytochrome P450 2D6P10635HumansPredicted (SEA)2103.17
Click to view 3D structureIsopentenyl-diphosphate Delta-isomerase 1O35760Rattus norvegicusPredicted (SEA)0.778492
Click to view 3D structureFarnesyl pyrophosphate synthaseP05369Rattus norvegicusPredicted (SEA)0.778492
Click to view 3D structureThromboxane-A synthaseP24557HumansPredicted (SEA)61.7344
Cytochrome P450 1A2 structureClick to view 3D structureCytochrome P450 1A2P05177HumansPredicted (SEA)2262.22
Click to view 3D structureHeme oxygenase 2P23711Rattus norvegicusPredicted (SEA)8.64126
Farnesyl pyrophosphate synthase structureClick to view 3D structureFarnesyl pyrophosphate synthaseP14324HumansKnownThe action of zoledronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Zoledronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates such as zoledronate appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Geranylgeranyl pyrophosphate synthase structureClick to view 3D structureGeranylgeranyl pyrophosphate synthaseO95749HumansKnownNot Available
Matrix metalloproteinase-14 structureClick to view 3D structureMatrix metalloproteinase-14P50281HumansKnownNot Available
Concentrations
Not Available
External Links
DrugBank IDDB00399
HMDB IDHMDB0014543
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDZOL
Wikipedia LinkZoledronic_Acid
Chemspider ID61986
ChEBI ID46557
PubChem Compound ID68740
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Judith Aronhime, Revital Lifshitz-Liron, “Zoledronic acid crystal forms, zoledronate sodium salt crystal forms, amorphous zoledronate sodium salt, and processes for their preparation.” U.S. Patent US20050054616, issued March 10, 2005.

MSDSLink
General References
1. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ: Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61.
2. Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005 Jul 7;353(1):99-102; discussion 99-102.
3. Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S: Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007 Nov 1;357(18):1799-809. doi: 10.1056/NEJMoa074941. Epub 2007 Sep 17.