CAS 118072-93-8|Zomera|zoledronate|[1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid|Aclasta and Reclast|Zometa|Zoledronic Acid|Aclasta|Reclast |Zometa Concentrate|Zometa|Zoledronate|...

General Information

Structure

Molecular Formula

C₅H₁₀N₂O₇P₂

Molecular Mass

272.089622

Exact Mass

271.99632393

Charge

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

Canonic Smiles

OP(=O)(C(P(=O)(O)O)(Cn1cncc1)O)O

Isomeric Smiles

P(=O)(O)(O)C(P(=O)(O)O)(O)Cn1ccnc1

Calculated Properties

JChem

LogD (pH = 7.4)

-7.39

LogD (pH = 5.5)

-6.74

Log P

-3.85

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

0.66

Polar Surface Area

153.11

Polarizability

20.10

Molar Refractivity

52.16

LOG S

3.30

Data Source

Names and Identifiers

Synonyms

ZomeraAclasta and ReclastZometaZoledronic AcidZoledronateZoledronic acidZOLZoledronic Acid(1-hydroxy-2-(1h-imidazol-1-yl)-ethylidene)bisphosphonic acid(1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acidZOLzoledronic acidZOLEDRONIC ACID(1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid

IUPAC Traditional name

zoledronate [1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid

IUPAC name

[1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid

Brand Name

AclastaReclast Zometa ConcentrateZometaReclast

International Nonproprietary Name (INN)

zoledronic acid

Names and Identifiers

Registration numbers

PubChem CID

68740

PubChem SID

1609637454650731053801236

CAS Number

118072-93-8

CompTox Database

DTXSID0042668

Protein Data Bank

2f9k2f8c3ez32q583ldw4p0v6g312f8z2e914p0w1zw53iba4kfa3n464kq53n45

Patent number

EP1566177US2002165255WO2005110994US2008214545US2006258661EP1591122US2007238707WO2005047282WO2005046318WO2006097323EP0911321EP1972341WO2005025572US2007196464

BKMS React Database

BindingDB Database

DrugBank ID

PubMed Central

BRENDA Ligand Database

6184189166

PubMed Citation Links

33908127343418333432443034393156189829151532430934081204151613271218366319751105345854433441305034157824345607341769195234475752

Reactom Database

R-HSA-9717841

Beilstein Number

9205049

ArrayExpress (Gene Expression Altlas)

E-GEOD-33552

BRENDA Database

2.5.1.292.5.1.13.4.24.172.7.1.902.4.1.473.1.3.12.5.1.102.5.1.90

SureChEMBL Database

SCHEMBL19054

MetaboLights Database

MTBLS1642MTBLS2633MTBLS3750

Chemspider ID

KEGG DRUG Database

ACToR Database

CHEMBL

PDBeChem Database

Drug Central Database

CHEBI ID

Wikipedia Title

Gmelin ID

SABIO-RK Database

Registration numbers

Properties

Physical Property

Hydrophobicity(logP)

-4.2

Solubility

Sparingly soluble

sterile water

Product Information

Salt Data

Free Base

Application(s)

Prevents skeletal fractures in patients with multiple myeloma and prostate cancer

Purity

97%

Safety Information

Storage Condition

-20°C

Pharmacology Properties

Target

PKC

Mechanism of Action

Human gamma-lambda T cells activator

Bone resorption inhibitor

Calcium regulator

Properties

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00399

Drug Groups

approved

Description

Zoledronate (zoledronic acid, marketed by Novartis under the trade names Zometa and Reclast) is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases.

An annual dose of Zoledronate may also prevent recurring fractures in patients with a previous hip fracture.

Zoledronate is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis.

Indication

For the treatment of hypercalcemia of malignancy. Also for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. In May of 2007, the drug was approved for treatment of Paget’s Disease.

Pharmacology

Zoledronate is a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronate is used to prevent osteoporosis and skeletal fractures, particularly in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia, particularly hypercalcemia of malignancy. It can also be helpful for treating pain from bone metastases.

Toxicity

There 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.

Affected Organisms

Humans and other mammals

Biotransformation

Zoledronate does not inhibit human P450 enzymes in vitro and does not undergo biotransformation in vivo.

Absorption

Poorly absorbed (oral absorption is about 1% of what intravenous absorption is).

Half Life

146 hours

Protein Binding

Approximately 22% bound in human plasma, independent of the concentration. However, Canadian product information states binding to human plasma protein is approximately 56%.

Elimination

In 64 patients with cancer and bone metastases, on average (± s.d.) 39 ± 16% of the administered zoledronic acid dose was recovered in the urine within 24 hours, with only trace amounts of drug found in urine post-Day 2.

Clearance

* Renal cl=3.7 +/- 2.0 L/h

References

• 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 Sep 26;. [Pubmed]

• 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. [Pubmed]

• 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. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

Selleck Chemicals

S1314

Research Area: Cancer
Biological Activity:
Zoledronic acid, one of the most potent nitrogen-containing BPs(bisphosphonates), induces antiproliferative and apoptotic effects on multiple myeloma cell lines in vitro, by activating protein kinase C, and increases the extracellular calcium concentration.Zoledronic acid and radiation caused a dosedependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). [1]Zoledronate is also known as zometa. It is a treatment for hypercalcemia (high levels of calcium in the blood) caused by tumors. Tumor-induced hypercalcemia is also known as hyper-calcemia of malignancy (HCM). [2]Zoledronic acid also inhibited proliferation of human foetal osteoblastic cell line (hFOB) with an IC50 of 40 μM.In cultures of freshly isolated rabbit and human osteoclasts zoledronic acid (10-100 μM) induced morphological features similar to apoptosis and caspase-3-like activation. Osteoclastogenesis was inhibited in a dose-dependent manner with an IC50 of 15 nM in vitro in cultures of murine bone marrow cells stimulated to form osteoclasts by addition of macrophage-colony stimulating factor and ligand for the receptor activator NF-κB (RANKL).

ChEBI

CHEBI:46557

An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.

Molecule Details

References

PubChem Literature

From Data Sources

• 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. Pubmed

• http://priory.com/pharmol/zoledronic_acid.htm

• Berenson, J.R. et al., Cancer (Philadelphia), 2001, 91, 144-154, (pharmacol)

• Dunford, J.E. et al., J. Pharmacol. Exp. Ther., 2001, 296, 235-242, (pharmacol)

• Green, J.R. et al., J. Bone Min. Res., 1994, 9, 745, (pharmacol)

• U.S. Pat., 1990, Ciba-Geigy, 4 939 130; CA, 114, 62355a, (synth, pharmacol)

• Sorbera, L.A. et al., Drugs of the Future, 2000, 25, 259-268, (rev)

• Cheer, S.M. et al., Drugs, 2001, 61, 799-805, (rev)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

Synonyms

IUPAC Traditional name

zoledronate [1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid

IUPAC name

[1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid

Brand Name

AclastaReclast Zometa ConcentrateZometaReclast

International Nonproprietary Name (INN)

zoledronic acid

Properties

Physical Property

Hydrophobicity(logP)

-4.2

Solubility

Sparingly soluble

sterile water

Product Information

Salt Data

Free Base

Application(s)

Prevents skeletal fractures in patients with multiple myeloma and prostate cancer

Purity

97%

Safety Information

Storage Condition

-20°C

Pharmacology Properties

Target

PKC

Mechanism of Action

Human gamma-lambda T cells activator

Bone resorption inhibitor

Calcium regulator

References

PubChem Literature

From Data Sources

• 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. Pubmed

• http://priory.com/pharmol/zoledronic_acid.htm

• Berenson, J.R. et al., Cancer (Philadelphia), 2001, 91, 144-154, (pharmacol)

• Dunford, J.E. et al., J. Pharmacol. Exp. Ther., 2001, 296, 235-242, (pharmacol)

• Green, J.R. et al., J. Bone Min. Res., 1994, 9, 745, (pharmacol)

• U.S. Pat., 1990, Ciba-Geigy, 4 939 130; CA, 114, 62355a, (synth, pharmacol)

• Sorbera, L.A. et al., Drugs of the Future, 2000, 25, 259-268, (rev)

• Cheer, S.M. et al., Drugs, 2001, 61, 799-805, (rev)

Bioactivity

PubChem BioAssay

Registration numbers

PubChem CID

68740

PubChem SID

1609637454650731053801236

CAS Number

118072-93-8

CompTox Database

DTXSID0042668

Protein Data Bank

2f9k2f8c3ez32q583ldw4p0v6g312f8z2e914p0w1zw53iba4kfa3n464kq53n45

Patent number

EP1566177US2002165255WO2005110994US2008214545US2006258661EP1591122US2007238707WO2005047282WO2005046318WO2006097323EP0911321EP1972341WO2005025572US2007196464

BKMS React Database

BindingDB Database

DrugBank ID

PubMed Central

BRENDA Ligand Database

6184189166

PubMed Citation Links

33908127343418333432443034393156189829151532430934081204151613271218366319751105345854433441305034157824345607341769195234475752

Reactom Database

R-HSA-9717841

Beilstein Number

9205049

ArrayExpress (Gene Expression Altlas)

E-GEOD-33552

BRENDA Database

2.5.1.292.5.1.13.4.24.172.7.1.902.4.1.473.1.3.12.5.1.102.5.1.90

SureChEMBL Database

SCHEMBL19054

MetaboLights Database

MTBLS1642MTBLS2633MTBLS3750

Chemspider ID

KEGG DRUG Database

ACToR Database

CHEMBL

PDBeChem Database

Drug Central Database

CHEBI ID

Wikipedia Title

Gmelin ID

SABIO-RK Database

Molecule Details

DB00399

Drug Groups

approved

Description

Indication

Pharmacology

Toxicity

Affected Organisms

Humans and other mammals

Biotransformation

Zoledronate does not inhibit human P450 enzymes in vitro and does not undergo biotransformation in vivo.

Absorption

Poorly absorbed (oral absorption is about 1% of what intravenous absorption is).

Half Life

146 hours

Protein Binding

Approximately 22% bound in human plasma, independent of the concentration. However, Canadian product information states binding to human plasma protein is approximately 56%.

Elimination

Clearance

* Renal cl=3.7 +/- 2.0 L/h

References

• 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. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

Selleck Chemicals

S1314

ChEBI

CHEBI:46557

An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.

Molecule

ID:282