Details
Stereochemistry | ACHIRAL |
Molecular Formula | C6H14N2O2.C5H10N2O7P2.H2O |
Molecular Weight | 436.2925 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.NCCCCC(N)C(O)=O.OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O
InChI
InChIKey=MLPSARXCSRWMAC-UHFFFAOYSA-N
InChI=1S/C6H14N2O2.C5H10N2O7P2.H2O/c7-4-2-1-3-5(8)6(9)10;8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7;/h5H,1-4,7-8H2,(H,9,10);1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14);1H2
Molecular Formula | H2O |
Molecular Weight | 18.0153 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C5H10N2O7P2 |
Molecular Weight | 272.0896 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C6H14N2O2 |
Molecular Weight | 146.1876 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
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 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22390415 |
4.1 nM [IC50] | ||
Target ID: CHEMBL4769 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17535895 |
97.0 µM [IC50] | ||
Target ID: CHEMBL3510 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24813742 |
92.0 nM [IC50] | ||
Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24650641 |
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021817s000_PharmR_P1.pdf#page=50 Page: 50.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no |
PubMed
Title | Date | PubMed |
---|---|---|
Zoledronic acid: an evolving role in the treatment of cancer patients with bone disease. | 2001 Apr |
|
Zoledronic acid in the treatment of hypercalcemia of malignancy: results of the international clinical development program. | 2001 Apr |
|
The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. | 2001 Apr |
|
Chemical and biological prerequisites for novel bisphosphonate molecules: results of comparative preclinical studies. | 2001 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 |
|
Adjuvant bisphosphonate therapy: the future. | 2001 Aug |
|
Dosing regimens and main adverse events of bisphosphonates. | 2001 Aug |
|
Should bisphosphonates be the treatment of choice for metastatic bone disease? | 2001 Aug |
|
Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. | 2001 Feb |
|
[Tumor-induced hypercalcemia. Review of bisphosphonate treatment]. | 2001 Jul |
|
Safety and efficacy of bisphosphonates beyond 24 months in cancer patients. | 2001 Jul 15 |
|
Metastatic bone disease and tumour-induced hypercalcaemia: the role of bisphosphonates. | 2001 Jun |
|
A phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases. | 2001 Mar |
|
[Bone metastasis. Can a new bisphosphonate offer control?]. | 2001 Mar 1 |
|
Advances in the biology and treatment of myeloma bone disease. | 2001 Nov 15 |
|
Paget's disease of the spine and its management. | 2001 Oct |
|
New bisphosphonic acid approved by FDA. | 2001 Oct 1 |
|
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 |
|
Actions of bisphosphonates in animal models of breast cancer. | 2002 |
|
Development of bisphosphonates. | 2002 |
|
The present and future role of bisphosphonates in the management of patients with breast cancer. | 2002 |
|
Direct effects of bisphosphonates on breast cancer cells. | 2002 |
|
FDA approves ZOMETA for treatment of cancer-related bone complications. | 2002 Apr |
|
Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia? | 2002 Apr 22 |
|
Bisphosphonates: biological response modifiers in breast cancer. | 2002 Aug |
|
Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). | 2002 Aug 15 |
|
The anti-tumour activity of bisphosphonates. | 2002 Dec |
|
The role of osteoclastic activity in prostate cancer skeletal metastases. | 2002 Feb |
|
Intravenous zoledronic acid in postmenopausal women with low bone mineral density. | 2002 Feb 28 |
|
Bisphosphonates and osteoporosis. | 2002 Feb 28 |
|
Multiple myeloma: present and future. | 2002 Jan |
|
Osteoporosis: challenges and new opportunities for therapy. | 2002 Jul |
|
Bisphosphonates for cancer patients: why, how, and when? | 2002 Jul |
|
Zoledronate once-yearly increases bone mineral density--implications for osteoporosis. | 2002 Jul |
|
Electrolyte abnormalities with zoledronic acid therapy. | 2002 Jul-Aug |
|
Novel approaches to the management of bone metastases in patients with breast cancer. | 2002 Jun |
|
Treatment of malignant hypercalcaemia. | 2002 May |
|
Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. | 2002 Nov 15 |
|
Development and validation of a highly sensitive RIA for zoledronic acid, a new potent heterocyclic bisphosphonate, in human serum, plasma and urine. | 2002 Nov 7 |
|
Bisphosphonate therapy in multiple myeloma: past, present, future. | 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 |
|
[Bisphosphonates in bone metastases. Fewer fractures, less pain]. | 2002 Sep 26 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26126921
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).
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 14:05:43 GMT 2023
by
admin
on
Sat Dec 16 14:05:43 GMT 2023
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Record UNII |
IL1N7FSO1U
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Record Status |
Validated (UNII)
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Record Version |
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-
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Name | Type | Language | ||
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Common Name | English |
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FDA ORPHAN DRUG |
461014
Created by
admin on Sat Dec 16 14:05:43 GMT 2023 , Edited by admin on Sat Dec 16 14:05:43 GMT 2023
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Code System | Code | Type | Description | ||
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IL1N7FSO1U
Created by
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PRIMARY | |||
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1323976-37-9
Created by
admin on Sat Dec 16 14:05:43 GMT 2023 , Edited by admin on Sat Dec 16 14:05:43 GMT 2023
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NON-SPECIFIC STOICHIOMETRY | |||
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91826755
Created by
admin on Sat Dec 16 14:05:43 GMT 2023 , Edited by admin on Sat Dec 16 14:05:43 GMT 2023
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PRIMARY |