Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | 2C5H10N2O7P2.5H2O |
| Molecular Weight | 634.2556 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.O.O.O.O.OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O.OC(CN2C=CN=C2)(P(O)(O)=O)P(O)(O)=O
InChI
InChIKey=AZZILOGHCMYHQY-UHFFFAOYSA-N
InChI=1S/2C5H10N2O7P2.5H2O/c2*8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7;;;;;/h2*1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14);5*1H2
Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved
bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1782 |
4.1 nM [IC50] | ||
Target ID: CHEMBL4769 |
97.0 µM [IC50] | ||
Target ID: CHEMBL3510 |
92.0 nM [IC50] | ||
Target ID: CHEMBL205 |
62.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
|||
| Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
|||
| Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
|||
| Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
|||
| Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated dequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
264 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21563999 |
4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
ZOLEDRONIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
420 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21563999 |
4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
ZOLEDRONIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
39 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21563999 |
4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
ZOLEDRONIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
16 mg 1 times / 4 weeks multiple, intravenous Highest studied dose Dose: 16 mg, 1 times / 4 weeks Route: intravenous Route: multiple Dose: 16 mg, 1 times / 4 weeks Sources: |
unhealthy, 40-79 years n = 12 Health Status: unhealthy Condition: cancer Age Group: 40-79 years Sex: M+F Population Size: 12 Sources: |
|
16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
Other AEs: Skeletal pain, Fever... Other AEs: Skeletal pain (30%) Sources: Fever (20%) Anorexia (20%) Diarrhea (20%) Constipation (10%) Nausea (20%) Myalgia (20%) Arthralgia (10%) Anemia (30%) Rigors (20%) Coughing (20%) Leg edema (10%) Urinary tract infection (10%) Fatigue (40%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Arthralgia | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Constipation | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Leg edema | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Urinary tract infection | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Anorexia | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Coughing | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Diarrhea | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Fever | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Myalgia | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Nausea | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Rigors | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Anemia | 30% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Skeletal pain | 30% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
| Fatigue | 40% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) n = 10 Health Status: unhealthy Condition: cancer Age Group: 54 years (range: 34–73 years) Sex: M+F Population Size: 10 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Bisphosphonates induce apoptosis in human breast cancer cell lines. | 2000 Apr |
|
| The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. | 2001 Apr 20 |
|
| [Bisphosphonates in the treatment of breast carcinoma]. | 2001 Aug |
|
| Dosing regimens and main adverse events of bisphosphonates. | 2001 Aug |
|
| Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. | 2001 Jan 15 |
|
| A phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases. | 2001 Mar |
|
| Bisphosphonate treatment inhibits the growth of prostate cancer cells. | 2001 Mar 15 |
|
| Conventional treatment of hypercalcemia of malignancy. | 2001 Nov 15 |
|
| FDA grants priority review for ZOMETA. | 2001 Oct |
|
| Bisphosphonates for osteoporosis. | 2001 Sep |
|
| The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. | 2002 |
|
| U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. | 2002 |
|
| Bisphosphonates: biological response modifiers in breast cancer. | 2002 Aug |
|
| The role of osteoclastic activity in prostate cancer skeletal metastases. | 2002 Feb |
|
| Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. | 2002 Feb |
|
| Intravenous zoledronic acid in postmenopausal women with low bone mineral density. | 2002 Feb 28 |
|
| Osteoporosis: challenges and new opportunities for therapy. | 2002 Jul |
|
| Zoledronate once-yearly increases bone mineral density--implications for osteoporosis. | 2002 Jul |
|
| Zoledronic acid. A bisphosphonate for hypercalcemia of malignancy and osteolytic metastases. | 2002 Jul-Aug |
|
| Novel approaches to the management of bone metastases in patients with breast cancer. | 2002 Jun |
|
| Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. | 2002 Mar |
|
| Severe increase in creatinine with hypocalcaemia in thalidomide-treated myeloma patients receiving zoledronic acid infusions. | 2002 Nov |
|
| Zoledronic acid improves the mechanical properties of normal and healing bone. | 2002 Nov-Dec |
|
| Gateways to clinical trials. | 2002 Oct |
|
| Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severe-combined-immunodeficient mouse model. | 2002 Oct 1 |
|
| Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. | 2002 Sep |
Patents
Sample Use Guides
The maximum recommended dose of Zometa in hypercalcemia of malignancy is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes.
Route of Administration:
Intravenous
For the transfection of the T24 human bladder cancer cells, pCMV6 empty vector (OriGene, Rockville, MD, USA) and pCMV6 TAp73 vector were transfected into cells using Lipofectamine™ 2000 (Invitrogen Life Technologies). After 6 h, the medium was refreshed and cultured for 48 h. Then the cells were treated with ZA (200 μM).
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SUB178554
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72734361
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DBSALT001962
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1K9U67HDID
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100000164225
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PARENT (SALT/SOLVATE)
SUBSTANCE RECORD
