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 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 |
---|---|---|
[Bisphosphonates in the treatment of breast carcinoma]. | 2001 Aug |
|
Zolendronate (zometa). | 2001 Dec 10 |
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Metastatic bone disease and tumour-induced hypercalcaemia: the role of bisphosphonates. | 2001 Jun |
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Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions. | 2001 Nov |
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Conventional treatment of hypercalcemia of malignancy. | 2001 Nov 15 |
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Advances in the biology and treatment of myeloma bone disease. | 2001 Nov 15 |
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FDA grants priority review for ZOMETA. | 2001 Oct |
|
Paget's disease of the spine and its management. | 2001 Oct |
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Bisphosphonates for osteoporosis. | 2001 Sep |
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The use of zoledronic acid, a novel, highly potent bisphosphonate, for the treatment of hypercalcemia of malignancy. | 2002 |
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The role of bisphosphonates in breast cancer management: review article. | 2002 |
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FDA approves ZOMETA for treatment of cancer-related bone complications. | 2002 Apr |
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Bisphosphonates: biological response modifiers in breast cancer. | 2002 Aug |
|
Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). | 2002 Aug 15 |
|
Advances in the biology and treatment of myeloma bone disease. | 2002 Dec |
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The anti-tumour activity of bisphosphonates. | 2002 Dec |
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Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain. | 2002 Dec |
|
Monosodium [1-hydroxy-2-(1H-imidazol-3-ium-4-yl)ethane-1,1-diyl]bis(phosphonate) tetrahydrate (monosodium isozoledronate). | 2002 Dec |
|
Pharmacological treatments for prostate cancer. | 2002 Dec |
|
The role of osteoclastic activity in prostate cancer skeletal metastases. | 2002 Feb |
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Distinct mechanisms of bisphosphonate action between osteoblasts and breast cancer cells: identity of a potent new bisphosphonate analogue. | 2002 Feb |
|
Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. | 2002 Feb |
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Multiple myeloma: present and future. | 2002 Jan |
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New drugs 2002, part III. | 2002 Jul |
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Osteoporosis: challenges and new opportunities for therapy. | 2002 Jul |
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Bisphosphonates for cancer patients: why, how, and when? | 2002 Jul |
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Novel therapeutic options for osteoporosis. | 2002 Jul |
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Zoledronate once-yearly increases bone mineral density--implications for osteoporosis. | 2002 Jul |
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Adaptive dose finding for phase I clinical trials of drugs used for chemotherapy of cancer. | 2002 Jul 15 |
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An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs. | 2002 Jul 4 |
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Electrolyte abnormalities with zoledronic acid therapy. | 2002 Jul-Aug |
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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 |
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Bisphosphonates influence the proliferation and the maturation of normal human osteoblasts. | 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 |
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Treatment of malignant hypercalcaemia. | 2002 May |
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The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs membrane] localisation and induces cytochrome c release in breast cancer cells. | 2002 May 6 |
|
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 |
|
The use of bisphosphonates in patients with breast cancer. | 2002 Nov-Dec |
|
Bisphosphonate therapy in multiple myeloma: past, present, future. | 2002 Nov-Dec |
|
Zoledronic acid improves the mechanical properties of normal and healing bone. | 2002 Nov-Dec |
|
Zoledronic acid. | 2002 Nov-Dec |
|
Gateways to clinical trials. | 2002 Oct |
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Zoledronic acid: new preparation. Just a me-too: no advance in hypercalcemia of malignancy. | 2002 Oct |
|
Intravenous zoledronic acid in postmenopausal women with low bone mineral density. | 2002 Oct |
|
The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells. | 2002 Oct |
|
Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severe-combined-immunodeficient mouse model. | 2002 Oct 1 |
|
A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. | 2002 Oct 2 |
|
Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. | 2002 Sep |
|
American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. | 2002 Sep 1 |
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).
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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
Created by
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PARENT (SALT/SOLVATE)
SUBSTANCE RECORD