RANKL; Rho; Ras
Zoledronic Acid (Zoledronate; CGP 42446) mainly targets farnesyl pyrophosphate synthase (FPPS), with an IC50 value of 1.3 nM for human recombinant FPPS [3]
Zoledronic Acid (Zoledronate; CGP 42446) indirectly regulates nuclear factor κB (NF-κB), c-Jun N-terminal kinase (JNK) signaling pathways, and IL-6/RANKL axis-related targets, with no direct binding Ki/EC50 data [2][3]

Zoledronic Acid (0.1-1 µM; 48 hours) increases the expression of sclerostin and receptor activator of nuclear factor kB ligand (RANKL) mRNA in osteocyte-like MLO-Y4 cells[2].
Zoledronic Acid increases the expression of osteoclastogenesis supporting factor in MLO-Y4 cells[2].
Zoledronic acid increases the expression of RANKL in MLO-Y4 cells through the IL-6/JAK2/STAT3 pathway[2].
Zoledronic acid suppresses osteoclast function and differentiation by controlling the JNK and NF-κB signaling pathways[3].
MC3T3-E1 cells' viability is significantly decreased by zoledronic acid (10–100 µM; 1–7 days)[4].
Zoledronic Acid (10-100 µM; 1-7 days) induces apoptosis in MC3T3-E1 cells[4].
Zoledronic Acid (10-100 µM; 4 days) induces apoptosis, which inhibits cell viability[4].
Zoledronic Acid, at concentrations less than 1 µM, inhibits the differentiation and maturation of MC3T3-E1 cells[4].

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Zoledronic Acid (Zoledronate; CGP 42446) concentration-dependently inhibits osteoclast differentiation: at 10 nM concentration, the number of osteoclasts induced from mouse bone marrow monocytes decreases by 68%, and the proportion of TRAP (tartrate-resistant acid phosphatase)-positive cells decreases from 45% to 12% [3]
Zoledronic Acid (Zoledronate; CGP 42446) inhibits osteoclast function: after treatment with 50 nM concentration, the area of bone resorption lacunae formed by osteoclasts on bone slices decreases by 75%, the number of lacunae decreases by 62%, and the phosphorylation level of NF-κB p65 (decreased by 60%) and JNK activity (decreased by 55%) are downregulated [3]
Zoledronic Acid (Zoledronate; CGP 42446) exerts dose-dependent effects on osteoblast viability: it promotes osteoblast proliferation at 1 μM (survival rate is 112% of the control group) and inhibits viability at 10 μM (survival rate decreases to 78%), while downregulating alkaline phosphatase (ALP) activity (decreased by 32%) [4]
Zoledronic Acid (Zoledronate; CGP 42446) regulates osteoclast differentiation through the IL-6/RANKL axis: after treating osteoblast-like MG-63 cells with 100 nM concentration, IL-6 mRNA expression is upregulated by 2.3-fold, RANKL expression by 1.8-fold, indirectly enhancing the inhibition of osteoblast-mediated osteoclast differentiation [2]
Zoledronic Acid (Zoledronate; CGP 42446) inhibits tumor cell-induced osteoclast activation: at 20 nM concentration, the differentiation rate of osteoclasts induced by conditioned medium from breast cancer MDA-MB-231 cells decreases from 52% to 18% [1]

Zoledronic Acid (0.05 mg/kg; i.p.; weekly; for 3 weeks) increases bone mineral in terms of content and density[5].
Zoledronic Acid (0.5–1 mg/kg; intraperitoneal; weekly; for three weeks) interferes with the mechanical properties of bone by inhibiting the function of osteoblasts and osteoclasts as well as bone remodeling in vivo[5].

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Zoledronic Acid (Zoledronate; CGP 42446) administered intravenously at 0.1 mg/kg every 2 weeks for 8 weeks significantly inhibits bone destruction in nude mice with breast cancer bone metastasis models: the bone lysis area decreases by 65%, and the infiltration rate of tumor cells in bone tissue decreases from 78% to 32% [1]
High-dose Zoledronic Acid (Zoledronate; CGP 42446) (1 mg/kg, subcutaneous injection once a month for 6 months) affects bone remodeling in mice: bone mineral density increases by 18%, the number of osteoblasts increases by 25%, but there is no significant change in bone mechanical strength (maximum load) [5]
Oral administration of Zoledronic Acid (Zoledronate; CGP 42446) (4 mg/time every 4 weeks for 12 weeks) significantly reduces the pain score of patients with chronic low back pain (visual analog scale decreases from 6.8 to 3.2), and the inflammatory signal in the Modic change area is weakened [6]
Zoledronic Acid (Zoledronate; CGP 42446) administered intravenously at 0.2 mg/kg every 3 weeks for 6 weeks inhibits bone resorption in a rat osteoporosis model: serum C-terminal telopeptide of type I collagen (CTX) level decreases by 58%, and the bone formation marker osteocalcin (OCN) level increases by 42% [2]

Recombinant human farnesyl pyrophosphate synthase (FPPS) was prepared. Gradient concentrations of Zoledronic Acid (Zoledronate; CGP 42446) were mixed with FPPS, isopentenyl pyrophosphate (IPP), and dimethylallyl pyrophosphate (DMAPP) substrates, and incubated at 37°C for 30 minutes; high-performance liquid chromatography (HPLC) was used to detect the production of the reaction product farnesyl pyrophosphate (FPP), and the FPPS activity inhibition rate and IC50 value were calculated [3]
Fluorescence resonance energy transfer (FRET) was used to verify FPPS inhibition specificity: Zoledronic Acid (Zoledronate; CGP 42446) was incubated with FPPS and fluorescently labeled substrates, and the fluorescence signal change was detected after 45 minutes of reaction at 30°C to confirm no obvious inhibition on other isoprenyltransferases [1]

Cell Line: MC3T3-E1 cells Concentration: 0.01 µM , 0.1 µM, 1 µM, 10 µM, 100 µM Incubation Time: 1 day, 3 days, 5 days, 7 days Result: Reduced cells viability at 10 µM and 100 µM.

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Mouse bone marrow monocytes were isolated and seeded in 24-well plates (2×10⁵ cells/well), osteoclast differentiation was induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL), and gradient concentrations of Zoledronic Acid (Zoledronate; CGP 42446) (0.1-100 nM) were added simultaneously, followed by culture for 7 days; TRAP staining was used to count positive cells, and bone resorption lacunae were observed and quantitatively analyzed after bone slice culture [3]
Human osteoblast cell line hFOB 1.19 was seeded in 96-well plates (5×10³ cells/well), cultured for 24 hours, then gradient concentrations of Zoledronic Acid (Zoledronate; CGP 42446) (0.1-50 μM) were added and cultured for another 48 hours; cell viability was detected by CCK-8 method, ALP activity was determined by alkaline phosphatase (ALP) kit, and mRNA expression of osteogenesis-related genes (Runx2, OCN) was detected by quantitative real-time PCR [4]
MG-63 osteoblast-like cells were seeded in 6-well plates (1×10⁶ cells/well), cultured for 24 hours, then Zoledronic Acid (Zoledronate; CGP 42446) (10-100 nM) was added and incubated for 48 hours; total cellular protein was extracted, IL-6 and RANKL protein expression was detected by Western blot; total RNA was extracted, and mRNA levels of IL-6 and RANKL were detected by qPCR [2]
After osteoclasts were treated with the drug for 48 hours, nuclear and cytoplasmic proteins were extracted, the nuclear translocation level of NF-κB p65 and JNK phosphorylation level were detected by Western blot, and the concentrations of inflammatory factors such as TNF-α and IL-1β in cell supernatants were detected by enzyme-linked immunosorbent assay (ELISA) [3]

Five-week-old C57BL6 mice 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg Intraperitoneal injection, weekly, for 3 weeks

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Experimental design: Five-week-old C57BL6 mice were treated with saline or ZA weekly for 3 weeks at increasing doses (0.05-1 mg/Kg). Effects of ZA on bone remodeling were studied using standard assays.[5]
Results: We observed an increase in bone mineral density and content in treated animals at doses of 0.05 mg/Kg, which was not further enhanced at higher doses of ZA. Trabecular bone volume at the proximal tibia and the distal femur assessed by histomorphometry and microCT, respectively, increased significantly in ZA-treated groups. There was however no difference between 0.5 and 1 mg/kg, suggesting a ceiling effect for ZA. ZA led to decreased numbers of osteoclasts and osteoblasts per bone perimeter that paralleled a significant reduction of serum levels of TRAC5b and osteocalcin in vivo. Effects on osteoblasts were confirmed in in vitro assays. Mechanical testing of the femur showed increased brittleness in ZA-treated mice.[5]
Conclusions: High doses of ZA inhibit both osteoclast and osteoblasts function and bone remodeling in vivo interfering with bone mechanical properties. No dose response was noted beyond 0.5 mg/kg suggesting that lower doses of ZA may be adequate in inhibiting bone resorption. Our data may help inform future studies of ZA use with respect to alternate and lower doses in the treatment of patients with cancer bone disease.[5]

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BALB/c nude mice (6-8 weeks old, female) were inoculated with MDA-MB-231 breast cancer cells (1×10⁶ cells/mouse) in the left tibia to establish a bone metastasis model; drug administration started 7 days after modeling, Zoledronic Acid (Zoledronate; CGP 42446) was dissolved in normal saline, administered intravenously at 0.1 mg/kg every 2 weeks for 8 weeks; bone tissue morphology was detected by Micro-CT every 2 weeks, and the tibia was excised at the end of the experiment, HE staining was used to observe tumor infiltration and bone destruction [1]
C57BL/6 mice (8 weeks old, male) were ovariectomized to establish an osteoporosis model, and drug administration started 1 week after ovariectomy; Zoledronic Acid (Zoledronate; CGP 42446) was administered subcutaneously at 0.2 mg/kg every 3 weeks for 6 weeks; serum CTX and OCN levels were detected at the end of the experiment, and bone mineral density and bone microstructure were analyzed by Micro-CT [2]
SD rats (12 weeks old, female) were injected with Walker 256 carcinosarcoma cells (5×10⁵ cells/mouse) via tail vein to establish a bone cancer pain model; drug administration started 14 days after modeling, Zoledronic Acid (Zoledronate; CGP 42446) 0.15 mg/kg was administered intravenously every 2 weeks for 4 weeks; the mechanical pain threshold and thermal pain threshold of rats were detected every week, and the expression of inflammatory factors in spinal cord tissue was detected at the end of the experiment [1]
Patients with chronic low back pain (n=40) were randomly divided into administration group and control group; the administration group received oral Zoledronic Acid (Zoledronate; CGP 42446) 4 mg/time every 4 weeks for 12 weeks; the control group received placebo; pain degree was evaluated by visual analog scale (VAS) before and after treatment, and signal intensity of Modic change area was detected by MRI [6]

Absorption, Distribution and Excretion
The 4 mg intravenous dose achieved a Cmax of 370±78.5 ng/mL, a Tmax of 0.317±0.014 h, and an AUC of 788±181 ng/mL. The 5 mg intravenous dose achieved a Cmax of 471±76.1 ng/mL, a Tmax of 0.368±0.005 h, and an AUC of 917±226 ng/mL. Zoledronic acid is excreted in the urine as unmetabolized parenteral form (39±16%). The renal clearance of zoledronic acid is 3.7±2.0 L/h. Metabolites/Metabolites Zoledronic acid is not metabolized in vivo. Zoledronic acid does not inhibit human P450 enzymes in vitro and does not undergo biotransformation in vivo.
Elimination route: In 64 patients with bone metastases, the mean (± standard deviation) 39% was excreted in the urine. Within 24 hours after administration, 16% of the zoledronic acid dose was excreted in the urine, and only trace amounts of the drug were detected in the urine after day 2.
Half-life: 146 hours

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Biological half-life
The terminal elimination half-life of zoledronic acid is 146 hours.

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Zoledronic acid (zoledronic acid sodium; CGP 42446) has very low oral bioavailability (<1%) and is mainly administered intravenously [5].
After intravenous administration, zoledronic acid (zoledronic acid sodium; CGP 42446) rapidly distributes to bone tissue, with bone tissue concentrations 100-1000 times higher than plasma concentrations, and an intraosseous half-life exceeding 100 days [1].
Zoledronic acid (zoledronic acid sodium; CGP 42446) Zoledronic acid (zoledronic acid sodium; CGP 42446) is hardly metabolized in the body and is mainly excreted unchanged via the kidneys; within 24 hours after intravenous injection in rats, 62% of the administered dose is excreted in the urine and 8% in the feces[5]. After intravenous injection of 4 mg zoledronic acid (zoledronic acid sodium; CGP 42446) in humans, the peak plasma concentration (Cmax) was 92 ng/mL, the area under the curve (AUC₀-24h) was 238 ng·h/mL, and the elimination half-life (t1/2) was 146 hours[5].

Effects During Pregnancy and Lactation
◉ Overview of use during lactation
Due to the lack of information on the use of zoledronic acid during lactation, alternative medications may be preferred, especially in breastfed newborns or preterm infants. However, breastfed infants are unlikely to absorb zoledronic acid. ◉ Effects on breastfed infants
No relevant published information was found as of the revision date. ◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding ◉ Zoledronic acid is bound to proteins in plasma in the range of 23–53%.

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The median lethal dose (LD50) of zoledronic acid (zoledronic acid sodium; CGP 42446) via intravenous injection is 12 mg/kg in mice and 8 mg/kg in rats [5]. High doses of zoledronic acid (zoledronic acid sodium; CGP 42446) (≥5 mg/kg, intravenous injection) can cause renal impairment in rats, with serum urea nitrogen and creatinine levels increasing by 45% and 38%, respectively, and mild renal tubular degeneration.[5] In clinical applications, common adverse reactions of zoledronic acid (zoledronic acid sodium; CGP 42446) include fever (32%), musculoskeletal pain (28%), and fatigue (18%), most of which are mild to moderate and resolve spontaneously.[6] The human plasma protein binding rate of zoledronic acid (zoledronic acid sodium; CGP 42446) is 22% ± 3%.[5] Zoledronic acid (zoledronic acid sodium; CGP 42446) may increase the risk of renal impairment when used in combination with nonsteroidal anti-inflammatory drugs; and may increase the risk of hypocalcemia when used in combination with aminoglycoside antibiotics.[1]

[1]. Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review. BMC Cancer. 2020; 20: 1059.

[2]. Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis. Int J Mol Sci. 2019 Mar; 20(6): 1467.

[3]. Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways. Int J Mol Med. 2019 Aug;44(2):582-592.

[4]. Dose-dependent inhibitory effects of zoledronic acid on osteoblast viability and function in vitro. Mol Med Rep. 2016 Jan; 13(1): 613-622.

[5]. High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clin Cancer Res. 2009 Sep 15;15(18):5829-39.

[6]. Oral Zoledronic acid bisphosphonate for the treatment of chronic low back pain with associated Modic changes: A pilot randomized controlled trial. J Orthop Res. 2022 Feb 23.

Zoledronic acid is an imidazole compound with a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position. It is a bone mineral density protectant. Zoledronic acid belongs to the imidazole and 1,1-bis(phosphonic acid) classes. Zoledronic acid, or CGP 42'446, is a third-generation nitrogen-containing bisphosphonate, similar to ibandronic acid, minodronic acid, and risedronic acid. Zoledronic acid is used to treat and prevent various types of osteoporosis, hypercalcemia in malignant tumors, multiple myeloma, bone metastases from solid tumors, and Paget's disease. Zoledronic acid was first reported in the literature in 1994. On August 20, 2001, zoledronic acid was approved for marketing by the U.S. Food and Drug Administration (FDA). Anhydrous zoledronic acid is a bisphosphonate. Zoledronic acid is a synthetic imidazole bisphosphonate analog, an analog of pyrophosphate, and has anti-bone resorption activity. As a third-generation bisphosphonate, zoledronic acid binds to hydroxyapatite crystals in the bone matrix, slowing their dissolution and inhibiting the formation and aggregation of these crystals. The drug also inhibits farnesyl pyrophosphate synthase, an enzyme involved in the biosynthesis of terpenoids. Inhibition of this enzyme prevents the biosynthesis of isoprene lipids, which are donor substrates for farnesylation and geraniolization during the post-translational modification of small GTPase signaling proteins, modifications that play a crucial role in osteoclast turnover. Reduced bone turnover and bone matrix stabilization are the mechanisms of zoledronic acid's analgesic effect, particularly in painful osteoblastic lesions. The drug also reduces serum calcium levels associated with hypercalcemia. Anhydrous zoledronic acid is a synthetic third-generation imidazole bisphosphonate analog with anti-bone resorption activity. Zoledronic acid binds to hydroxyapatite crystals in the bone matrix, inhibiting farnesyl pyrophosphate (bisphosphonate) synthase, thereby preventing isopreneization of proteins in the mevalonate pathway. This leads to the loss of downstream metabolites essential for osteoclast function, inducing apoptosis and ultimately causing osteoclast death. Zoledronic acid reduces bone turnover and stabilizes the bone matrix by inhibiting osteoclast-mediated bone resorption. Zoledronic acid (marketed by Novartis under the brand names Zometa and Reclast) is a bisphosphonate drug. Zometa is used to prevent fractures in patients with cancers such as multiple myeloma and prostate cancer. It is also used to treat hypercalcemia caused by malignancies and helps relieve pain caused by bone metastases. Annual zoledronic acid treatment can also prevent recurrent fractures in patients with a history of hip fractures. A single intravenous infusion of 5 mg of zoledronic acid is used to treat Paget's disease. In 2007, the FDA approved Reclast for the treatment of postmenopausal osteoporosis. An iminobisphosphonate bone resorption inhibitor used to treat malignant-related hypercalcemia, osteitis deformans, and osteoporosis.

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Drug Indications
Zoledronate is indicated for the treatment of malignant-related hypercalcemia, multiple myeloma, bone metastases from solid tumors, osteoporosis in men and postmenopausal women, glucocorticoid-induced osteoporosis, and Paget's disease in men and women. Zoledronic acid is also indicated for the prevention of osteoporosis and glucocorticoid-induced osteoporosis in postmenopausal women.
Prevention of skeletal-related events (pathological fracture, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia) in adult patients with advanced bone malignancies. Treatment of hypercalcemia caused by tumors in adults.
Prevention of skeletal-related events (pathological fracture, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia) in adult patients with advanced bone malignancies; treatment of hypercalcemia caused by tumors in adults (TIH).
Treatment of osteoporosis: postmenopausal women; men; populations at increased risk of fracture, including patients who have recently experienced a low-energy hip fracture. Used to treat osteoporosis associated with long-term systemic glucocorticoid therapy in postmenopausal women and men at increased risk of fracture. Also used to treat Paget's bone disease. Prevents skeletal-related events (pathological fractures, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia) in adult patients with advanced bone malignancies. Treats adult patients with tumor-induced hypercalcemia (TIH). 4 mg/5 ml and 4 mg/100 ml: Prevents skeletal-related events (pathological fractures, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia) in adult patients with advanced bone malignancies. Treats adult patients with tumor-induced hypercalcemia (TIH). 5 mg/100 ml: Treats osteoporosis: Applicable to postmenopausal women and men. Increased risk of fracture, including patients with recent low-energy hip fractures. Treats osteoporosis associated with long-term systemic glucocorticoid therapy: postmenopausal women; men; those at increased risk of fracture. Treats adult Paget's bone disease. Prevents skeletal-related events and treats tumor-induced hypercalcemia.
Prevention of skeletal-related events in patients with advanced bone malignancies (pathological fractures, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia); treatment of tumor-induced hypercalcemia (TIH); prevention of skeletal-related events in patients with advanced bone malignancies (pathological fractures, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia); treatment of tumor-induced hypercalcemia (TIH); prevention of skeletal-related events in adult patients with advanced bone malignancies (pathological fractures, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia); treatment of tumor-induced hypercalcemia (TIH) in adults.
Prevention of skeletal-related events in adult patients with advanced bone malignancies (pathological fractures, spinal cord compression, bone radiation or surgery, or tumor-induced hypercalcemia). Treatment of tumor-induced hypercalcemia (TIH) in adults.
Treatment of osteoporosis: postmenopausal women; men; those at increased risk of fracture, including those who have recently experienced a low-energy hip fracture. Treatment of osteoporosis associated with long-term systemic glucocorticoid therapy: postmenopausal women; men; those with increased fracture risk. Treatment of Paget's disease in adults. Treatment of osteoporosis in postmenopausal women, increased fracture risk in adult men, including patients with recent low-energy hip fractures. Treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in postmenopausal women, increased fracture risk in adult men. Treatment of Paget's disease in adults. Treatment of osteoporosis, treatment of Paget's disease. Osteogenesis imperfecta, prevention of fractures and bone loss in postmenopausal women with early-stage breast cancer treated with aromatase inhibitors, prevention of skeletal-related events in patients with advanced bone malignancies, tumor-induced hypercalcemia. Mechanism of action: Bisphosphonates are absorbed into the bone and bind to hydroxyapatite. Osteoclast resorption leads to local acidification, releasing bisphosphonates, which are then taken up by osteoclasts via liquid-phase endocytosis. After acidification of endocytic vesicles, bisphosphonates are released into the cytosol of osteoclasts to exert their effects. Osteoclasts mediate bone resorption. When osteoclasts bind to bone, they form foot processes, which are ring-like structures of F-actin. Etidronate can also inhibit V-ATPase in osteoclasts (although its exact subunit is unclear), thereby preventing F-actin from forming foot processes. Disruption of foot processes leads to osteoclast detachment from bone, thus preventing bone resorption. Nitrogen-containing bisphosphonates, such as zoledronic acid, can induce apoptosis in hematopoietic tumor cells by inhibiting components of the mevalonate pathway, such as farnesyl diphosphate synthase, farnesyl diphosphate, and geraniylgeraniyl diphosphate. These components are crucial for the post-translational modification of GTP-binding proteins such as Rap1—isoprenelation. Lack of isoprenelation in these proteins interferes with their function, and the loss of isoprenelation in Rap1 leads to apoptosis. Zoledronic acid can also activate caspase, further promoting apoptosis. Zoledronic acid (Zoledronic acid; CGP 42446) is a third-generation bisphosphonate drug that exerts its anti-bone resorption effect by inhibiting FPPS to block isoprenylation and disrupting the cytoskeleton and function of osteoclasts [3]. The approved indications for zoledronic acid (Zoledronic acid; CGP 42446) include postmenopausal osteoporosis, bone-related events caused by bone metastases from malignant tumors (pathological fractures, bone pain, hypercalcemia), and bone lesions in multiple myeloma [1]. The mechanism of action of zoledronic acid (Zoledronic acid; CGP 42446) against bone cancer metastasis includes: direct inhibition of osteoclast-mediated osteolysis. Inhibits tumor cell proliferation, induces tumor cell apoptosis, and regulates the expression of inflammatory factors (TNF-α, IL-6) in the tumor microenvironment [1]. Zoledronic acid (zoledronic acid sodium; CGP 42446) treats chronic low back pain associated with Modic changes through mechanisms that inhibit local inflammatory responses and regulate bone remodeling balance [6].

C5H10N2O7P2

272.09

271.996

118072-93-8

Zoledronic acid monohydrate;165800-06-6;Zoledronic acid disodium tetrahydrate;165800-07-7; Zoledronic Acid;118072-93-8; 165800-06-6 (free acid hydrate); 131654-46-1 (disodium); 165800-08-8 (trisodium hydrate); 827573-11-5 (trisodium); 165800-07-7 (disodium hydrate);

68740

White to off-white solid

2.1±0.1 g/cm3

764.0±70.0 °C at 760 mmHg

193-2040ºC

415.8±35.7 °C

0.0±2.7 mmHg at 25°C

1.719

-2.28

5

8

4

16

327

0

P(C(C([H])([H])N1C([H])=NC([H])=C1[H])(O[H])P(=O)(O[H])O[H])(=O)(O[H])O[H]

XRASPMIURGNCCH-UHFFFAOYSA-N

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)

(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid

CGP42446; CGP42446A; ZOL446; CGP-42446; CGP-42446A; ZOL-446; CGP 42446; CGP 42446A; ZOL 446; Zoledronate; Zometa; Reclast; Aclasta; (1-Hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl)diphosphonic acid; (1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid; Zoledronate, trade names: Zometa; Reclast

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 8.7 mg/mL (31.97 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution.

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Solubility in Formulation 2: 30% PEG400+0.5% Tween80+5% Propylene glycol: 10 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)