Denosumab
Identification
- Summary
Denosumab is a RANK ligand (RANKL) inhibitor used for the management of osteoporosis in patients at high risk for bone fractures.
- Brand Names
- Prolia, Xgeva
- Generic Name
- Denosumab
- DrugBank Accession Number
- DB06643
- Background
Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Chemically, it consists of 2 heavy and 2 light chains. Each light chain consists of 215 amino acids. Each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. FDA approved on June 1, 2010.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6404H9912N1724O2004S50
- Protein Average Weight
- 144700.0 Da
- Sequences
> Denosumab αOPGL-1 heavy chain sequence EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
> Denosumab αOPGL-1 light chain sequence EIVLTQSPGTLSLSPGERATLSCRASQSVRGRYLAWYQQKPGQAPRLLIYGASSRATGIP DRFSGSGSGTDFTLTISRLEPEDFAVFYCQQYGSSPRTFGQGTKVEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- Denosumab
- External IDs
- AMG-162
Pharmacology
- Indication
Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.
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- Contraindications & Blackbox Warnings
- Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.
- Pharmacodynamics
In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia.
- Mechanism of action
Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.
Target Actions Organism ATumor necrosis factor ligand superfamily member 11 antibodyHumans - Absorption
When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
25.4 days
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (≥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Denosumab is combined with Abatacept. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Denosumab. Adalimumab The risk or severity of adverse effects can be increased when Denosumab is combined with Adalimumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Denosumab. Aducanumab The risk or severity of adverse effects can be increased when Denosumab is combined with Aducanumab. Aldesleukin The risk or severity of adverse effects can be increased when Denosumab is combined with Aldesleukin. Alefacept The risk or severity of adverse effects can be increased when Denosumab is combined with Alefacept. Alemtuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Alemtuzumab. Alirocumab The risk or severity of adverse effects can be increased when Denosumab is combined with Alirocumab. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Denosumab. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Administer calcium supplement. Calcium supplements should be used as necessary to prevent hypocalcemia.
- Administer vitamin supplements. Vitamin D should be administered as necessary to complement calcium in preventing hypocalcemia.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Ranmark (Daiichi Sankyo)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Prolia Solution 60 mg / mL Subcutaneous Amgen Not applicable Not applicable Canada Prolia Injection, solution 60 mg/ml Subcutaneous Amgen Europe B.V. 2021-01-27 Not applicable EU Prolia Solution 60 mg / mL Subcutaneous Amgen 2010-08-12 Not applicable Canada Prolia Injection, solution 60 mg/ml Subcutaneous Amgen Europe B.V. 2021-01-27 Not applicable EU Prolia Injection, solution 60 mg/ml Subcutaneous Amgen Europe B.V. 2021-01-27 Not applicable EU Prolia Injection 60 mg/1mL Subcutaneous AMGEN INC 2010-06-05 Not applicable US Xgeva Injection 120 mg/1.7mL Subcutaneous AMGEN INC 2010-11-18 Not applicable US Xgeva Injection, solution 120 mg Subcutaneous Amgen Europe B.V. 2016-09-08 Not applicable EU Xgeva Injection, solution 120 mg Subcutaneous Amgen Europe B.V. 2016-09-08 Not applicable EU Xgeva Injection, solution 120 mg Subcutaneous Amgen Europe B.V. 2016-09-08 Not applicable EU
Categories
- ATC Codes
- M05BX04 — Denosumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Blood Proteins
- Bone Density Conservation Agents
- Cancer immunotherapy
- Drugs Affecting Bone Structure and Mineralization
- Drugs for Treatment of Bone Diseases
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Musculo-Skeletal System
- Proteins
- RANK Ligand Blocking Activity
- RANK Ligand Inhibitor
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 4EQZ6YO2HI
- CAS number
- 615258-40-7
References
- General References
- External Links
- KEGG Drug
- D03684
- PubChem Substance
- 347910354
- 993449
- ChEMBL
- CHEMBL1237023
- PharmGKB
- PA166048634
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Denosumab
- FDA label
- Download (226 KB)
- MSDS
- Download (97.5 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Supportive Care Bone Giant Cell Tumor 1 4 Active Not Recruiting Treatment Osteoporosis / Osteoporosis Fracture / Postmenopausal Osteoporosis 1 4 Active Not Recruiting Treatment Osteoporosis / Postmenopausal Osteoporosis 1 4 Completed Diagnostic Postmenopausal Osteoporosis / Type 2 Diabetes Mellitus 1 4 Completed Other Postmenopausal Osteoporosis 1 4 Completed Prevention Osteoarthritis in the Hip Joint 1 4 Completed Prevention Resorption, Bone 1 4 Completed Treatment Breast Cancer / Metastatic Cancer / Prostate Cancer 1 4 Completed Treatment Denosumab Allergy / Zoledronic Acid Allergy 1 4 Completed Treatment Metabolic Bone Disorder 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous 60 mg/1mL Injection, solution Parenteral; Subcutaneous 60 MG/ML Solution Subcutaneous 60 mg / mL Injection, solution Subcutaneous 60 mg/ml Solution Subcutaneous 60 mg Injection Subcutaneous Injection Subcutaneous 120 mg/1.7mL Injection, solution Parenteral; Subcutaneous 120 MG Solution Subcutaneous 120 mg / 1.7 mL Solution Subcutaneous 120 mg Injection, solution Subcutaneous Solution Subcutaneous Injection, solution Subcutaneous 120 mg Injection, solution 120 mg/1.7ml Injection, solution 60 mg/1ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2257247 No 2012-09-11 2018-04-15 Canada CA2274987 No 2012-01-24 2017-12-22 Canada CA2285746 No 2010-09-28 2018-04-15 Canada CA2400929 No 2011-05-31 2021-02-23 Canada CA2328140 No 2012-03-13 2019-05-13 Canada
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Tumor necrosis factor receptor superfamily binding
- Specific Function
- Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be...
- Gene Name
- TNFSF11
- Uniprot ID
- O14788
- Uniprot Name
- Tumor necrosis factor ligand superfamily member 11
- Molecular Weight
- 35477.81 Da
References
- Lipton A, Jun S: RANKL inhibition in the treatment of bone metastases. Curr Opin Support Palliat Care. 2008 Sep;2(3):197-203. doi: 10.1097/SPC.0b013e32830baac2. [Article]
- Westenfeld R, Ketteler M, Brandenburg VM: Anti-RANKL therapy--implications for the bone-vascular-axis in CKD? Denosumab in post-menopausal women with low bone mineral density. Nephrol Dial Transplant. 2006 Aug;21(8):2075-7. Epub 2006 May 15. [Article]
Drug created at March 19, 2008 16:43 / Updated at March 24, 2023 20:20