Denosumab (Synonyms: D03684; Denosumab; Denosumab (usan)) |
Catalog No.GC19535
One-Click Copy Product Info
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Denosumab is an IgG2 monoclonal antibody that targets the RANKL protein.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 615258-40-7
Sample solution is provided at 25 µL, 10mM.
Denosumab is an IgG2 monoclonal antibody that targets the RANKL protein. Denosumab binds and inhibits RANKL to block the RANK/NF-κB signaling pathway. This action suppresses osteoclast differentiation, activation, and survival, thereby reducing bone resorption. Denosumab can be used in research related to osteoporosis, solid tumor bone metastasis, giant cell tumor of bone, and malignant hypercalcemia[1-4].
In vitro, treatment of BRCA1mut/+ MCF10A cells with 100μg/mL Denosumab for 7 days significantly reduced the efficiency of mammosphere formation under suspension conditions and inhibited cell survival and proliferation ability[5]. Treatment of human pancreatic islet cells with 0.1μg/mL Denosumab for 24-72 hours increased the proportion of BrdU-positive human beta cells and increased the proportion of Ki67-positive human beta cells[6]. Addition of 0.1mg/mL Denosumab to a MCF-7 and RAW264.7 co-culture system for 5 days inhibited RAW264.7 cell differentiation into osteoclasts, reduced the number of TRAP-positive osteoclasts, downregulated MALAT1 expression, and upregulated miR-124 expression in RAW264.7 cells[7].
In vivo, subcutaneous injection of 10mg/kg Denosumab into C57BL/6J mice with destabilization of the medial meniscus once weekly for 4, 8, or 12 weeks reduced calcified cartilage layer thickness, lowered OARSI scores, inhibited synovial inflammatory cell infiltration and hyperplasia, reversed subchondral bone resorption, suppressed osteoclast activity, and increased mechanical pain thresholds[8]. Subcutaneous injection of 3mg/kg Denosumab into RANKL transgenic osteoporotic C57BL/6J mice once weekly for 18 weeks rescued the osteoporotic phenotype, increased femoral bone mineral density, restored distal femur trabecular bone volume fraction and bone mineral density, and reduced osteoclast number and osteoclast surface percentage[9]. A single intravenous injection of 120μg/mouse Denosumab via the retro-orbital venous plexus into humanized bone marrow/liver/thymus (hu-BLT) NSG mice increased IFN-γ secretion and NK cell-mediated cytotoxic activity in bone marrow mononuclear cells after IL-2 activation culture for 3 days, while decreasing IFN-γ secretion in peripheral blood mononuclear cells, splenocytes, pancreas, and post-extraction gingival tissues[10].
References:
[1] Jain S. Prevention and Management of Denosumab Discontinuation Rebound Fractures. Endocrinol Metab Clin North Am. 2024 Dec;53(4):559-583.
[2] Degboé Y, Couture G. Strategies for denosumab discontinuation in postmenopausal osteoporosis. Joint Bone Spine. 2026 Mar;93(2):105954.
[3] Bonnet N, Bourgoin L, Biver E, Douni E, et al. RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. Journal of Clinical Investigation. 2019 Aug;129(8):3214-3223.
[4] Bustamante-Gomez C, Fu Q, Goellner JJ, et al. Potent suppression of bone remodeling by denosumab does not blunt the anabolic response to romosozumab in mice. Bone. 2025 Oct;199:117567.
[5] Cuyas E, Corominas-Faja B, Munoz-San Martín M, et al. BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells. Oncotarget. 2017;8(21):35019-35032.
[6] Kondegowda NG, Fenutria R, Pollack I, et al. Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-KB Ligand (RANKL) Pathway. Cell Metabolism. 2015 Jul 7;22(1):77-85.
[7] Feng Q, Wang D, Feng J, et al. Denosumab inhibits MCF-7 cell line-induced spontaneous osteoclastogenesis via the RANKL/MALAT1/miR-124 axis. Translational Cancer Research. 2020 Apr;9(4):2482-2491.
[8] Hu Y, Chen W, Lan S, et al. Denosumab attenuates knee osteoarthritis progression by inhibiting synovial inflammation via the RANK/TRAF6/FSTL1 signalling. Nature Communications. 2025 Dec 17;16:11394.
[9] Rinotas V, Ntouskou E-D, Dragolia M, et al. Modeling rebound bone loss following denosumab discontinuation and sequential zoledronate therapy in TgRANKL osteoporotic mice. Frontiers in Endocrinology. 2026 Feb 26;17:1783656.
[10] Kaur K, Sun Y, Kanayama K, et al. Augmentation of IFN-y by bone marrow derived immune cells in the presence of severe suppression of IFN-y in gingivae induced by zoledronic acid and denosumab in Hu-BLT mice model of ONJ. Frontiers in Endocrinology. 2023 Jan 20;14:1111627.
| Cell experiment [1]: | |
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Cell lines |
MCF10A BRCA1+/+ and MCF10A BRCA1mut/+ (human breast epithelial cells), HMLERshCntrl and HMLERshECad (human mammary epithelial cells), MCF10DCIS.com (human DCIS cells), MDA-MB-231 and SUM-159 (human claudin-low TNBC cells), MCF-7/neo and MCF-7/HER2 (human luminal breast cancer cells) |
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Preparation Method |
Cells were maintained in respective serum-free mammosphere medium (DMEM/F-12 with B27, EGF, FGFb, methylcellulose) or adherent medium. Cells were treated with Denosumab during 7-day mammosphere culture or with 3-day monolayer pretreatment followed by 7-day mammosphere culture without Denosumab; mammosphere-forming efficiency (MSFE, spheres >50μm) was counted, MTT reduction assay assessed monolayer viability. |
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Reaction Conditions |
100μg/mL; 3-7 days |
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Applications |
Denosumab lowered mammosphere-forming efficiency of BRCA1mut/+ MCF10A cells. Denosumab reduced mammosphere formation of HMLERshECad, MCF10DCIS.com, MDA-MB-231, SUM-159, and MCF-7/HER2 cells relative to untreated controls. |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6J mice (12-week-old) with destabilization of the medial meniscus (DMM), male C57BL/6J mice (18-month-old) as aged OA model, male Sprague-Dawley rats with mono-iodoacetate (MIA) injection |
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Preparation Method |
DMM mice and aged mice were subcutaneously injected with 10mg/kg Denosumab once weekly for 4, 8, or 12 weeks; MIA rats were subcutaneously injected with 10mg/kg Denosumab once weekly, synovium, subchondral bone, and main organs were collected for Safranin O/Fast Green, H&E, TRAP, micro-CT, immunohistochemistry, MRI, and von Frey assays. |
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Dosage form |
10mg/kg; s.c.; weekly for 4-12 weeks (mice) |
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Applications |
Denosumab retained proteoglycan in articular cartilage, reduced calcified cartilage thickness, lowered OARSI score, inhibited synovial inflammatory cell infiltration and synovial hyperplasia, reduced synovitis score, reversed subchondral bone resorption, inhibited osteoclast hyperactivity, reduced osteophyte formation and GDF5+ cell number, downregulated MMP-13 and ADAMTS5 while upregulating Col2a1 and Aggrecan in cartilage, elevated paw withdrawal threshold in DMM mice and MIA rats, partially reduced cartilage degeneration and OARSI score in 18-month-old mice, attenuated cartilage loss and synovial inflammation in MIA rats, lowered effusion-synovitis MRI score. |
References: [1] Cuyas E, Corominas-Faja B, Munoz-San Martín M, et al. BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells. Oncotarget. 2017;8(21):35019-35032. [2] Hu Y, Chen W, Lan S, et al. Denosumab attenuates knee osteoarthritis progression by inhibiting synovial inflammation via the RANK/TRAF6/FSTL1 signalling. Nature Communications. 2025 Dec 17;16:11394. | |
| Cas No. | 615258-40-7 | SDF | |
| Synonyms | D03684; Denosumab; Denosumab (usan) | ||
| Formula | C6404H9908N1724O2004S50 | M.Wt | 144716.86 |
| Solubility | Storage | Store at 4°C, Do not freeze | |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.9 μL | 34.6 μL | 69.1 μL |
| 5 mM | 1.4 μL | 6.9 μL | 13.8 μL |
| 10 mM | 0.7 μL | 3.5 μL | 6.9 μL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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Purity: >99.50%
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- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)