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Identification
NameDenosumab
Accession NumberDB06643
TypeBiotech
GroupsApproved
Description

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.

Protein structureDb06643
Related Articles
Protein chemical formulaC6404H9912N1724O2004S50
Protein average weight144700.0 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
SynonymsNot Available
External Identifiers
  • AMG-162
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Proliainjection60 mg/mLsubcutaneousAmgen Inc2010-06-05Not applicableUs
Proliasolution60 mgsubcutaneousAmgen Canada IncNot applicableNot applicableCanada
Proliasolution60 mgsubcutaneousAmgen Canada Inc2010-08-12Not applicableCanada
Xgevasolution120 mgsubcutaneousAmgen Canada Inc2011-06-06Not applicableCanada
Xgevainjection120 mg/1.7mLsubcutaneousAmgen Inc2010-11-18Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
RanmarkDaiichi Sankyo
Brand mixturesNot Available
SaltsNot Available
Categories
UNII4EQZ6YO2HI
CAS number615258-40-7
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationProlia 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.
PharmacodynamicsIn 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 actionDenosumab 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.
Related Articles
AbsorptionWhen 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 distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life25.4 days
ClearanceNot Available
ToxicityIn 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
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injectionsubcutaneous60 mg/mL
Solutionsubcutaneous60 mg
Injectionsubcutaneous120 mg/1.7mL
Solutionsubcutaneous120 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2257247 No2012-09-112018-04-15Canada
CA2274987 No2012-01-242017-12-22Canada
CA2285746 No2010-09-282018-04-15Canada
CA2328140 No2012-03-132019-05-13Canada
CA2400929 No2011-05-312021-02-23Canada
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Malan J, Ettinger K, Naumann E, Beirne OR: The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec;114(6):671-6. doi: 10.1016/j.oooo.2012.08.439. [PubMed:23159111 ]
  2. Link [Link]
  3. Link [Link]
External Links
ATC CodesM05BX04
AHFS Codes
  • 92:24
PDB EntriesNot Available
FDA labelDownload (226 KB)
MSDSDownload (97.5 KB)
Interactions
Drug Interactions
Drug
AbataceptThe risk or severity of adverse effects can be increased when Denosumab is combined with Abatacept.
AdalimumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Adalimumab.
ado-trastuzumab emtansineThe risk or severity of adverse effects can be increased when Denosumab is combined with ado-trastuzumab emtansine.
AlemtuzumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Alemtuzumab.
AltretamineThe risk or severity of adverse effects can be increased when Denosumab is combined with Altretamine.
AmsacrineThe risk or severity of adverse effects can be increased when Denosumab is combined with Amsacrine.
AnakinraThe risk or severity of adverse effects can be increased when Denosumab is combined with Anakinra.
Anti-thymocyte Globulin (Rabbit)The risk or severity of adverse effects can be increased when Denosumab is combined with Anti-thymocyte Globulin (Rabbit).
AzacitidineThe risk or severity of adverse effects can be increased when Denosumab is combined with Azacitidine.
AzathioprineThe risk or severity of adverse effects can be increased when Denosumab is combined with Azathioprine.
BasilThe risk or severity of adverse effects can be increased when Denosumab is combined with Basil.
BasiliximabThe risk or severity of adverse effects can be increased when Denosumab is combined with Basiliximab.
BelataceptThe risk or severity of adverse effects can be increased when Denosumab is combined with Belatacept.
BelimumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Belimumab.
BetamethasoneThe risk or severity of adverse effects can be increased when Denosumab is combined with Betamethasone.
BleomycinThe risk or severity of adverse effects can be increased when Denosumab is combined with Bleomycin.
BlinatumomabThe risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab.
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Denosumab is combined with Brentuximab vedotin.
BudesonideThe risk or severity of adverse effects can be increased when Denosumab is combined with Budesonide.
BusulfanThe risk or severity of adverse effects can be increased when Denosumab is combined with Busulfan.
CabazitaxelThe risk or severity of adverse effects can be increased when Denosumab is combined with Cabazitaxel.
CanakinumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Canakinumab.
CapecitabineThe risk or severity of adverse effects can be increased when Denosumab is combined with Capecitabine.
CarboplatinThe risk or severity of adverse effects can be increased when Denosumab is combined with Carboplatin.
CarmustineThe risk or severity of adverse effects can be increased when Denosumab is combined with Carmustine.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Denosumab is combined with Certolizumab pegol.
ChlorambucilThe risk or severity of adverse effects can be increased when Denosumab is combined with Chlorambucil.
CisplatinThe risk or severity of adverse effects can be increased when Denosumab is combined with Cisplatin.
CladribineThe risk or severity of adverse effects can be increased when Denosumab is combined with Cladribine.
ClofarabineThe risk or severity of adverse effects can be increased when Denosumab is combined with Clofarabine.
CorticotropinThe risk or severity of adverse effects can be increased when Denosumab is combined with Corticotropin.
Cortisone acetateThe risk or severity of adverse effects can be increased when Denosumab is combined with Cortisone acetate.
CyclophosphamideThe risk or severity of adverse effects can be increased when Denosumab is combined with Cyclophosphamide.
CyclosporineThe risk or severity of adverse effects can be increased when Denosumab is combined with Cyclosporine.
CytarabineThe risk or severity of adverse effects can be increased when Denosumab is combined with Cytarabine.
DacarbazineThe risk or severity of adverse effects can be increased when Denosumab is combined with Dacarbazine.
DactinomycinThe risk or severity of adverse effects can be increased when Denosumab is combined with Dactinomycin.
DasatinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Dasatinib.
DaunorubicinThe risk or severity of adverse effects can be increased when Denosumab is combined with Daunorubicin.
DexamethasoneThe risk or severity of adverse effects can be increased when Denosumab is combined with Dexamethasone.
DinutuximabThe risk or severity of adverse effects can be increased when Denosumab is combined with Dinutuximab.
DocetaxelThe risk or severity of adverse effects can be increased when Denosumab is combined with Docetaxel.
DoxorubicinThe risk or severity of adverse effects can be increased when Denosumab is combined with Doxorubicin.
EculizumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Eculizumab.
EpirubicinThe risk or severity of adverse effects can be increased when Denosumab is combined with Epirubicin.
EstramustineThe risk or severity of adverse effects can be increased when Denosumab is combined with Estramustine.
EtanerceptThe risk or severity of adverse effects can be increased when Denosumab is combined with Etanercept.
EtoposideThe risk or severity of adverse effects can be increased when Denosumab is combined with Etoposide.
EverolimusThe risk or severity of adverse effects can be increased when Denosumab is combined with Everolimus.
FingolimodThe risk or severity of adverse effects can be increased when Denosumab is combined with Fingolimod.
FloxuridineThe risk or severity of adverse effects can be increased when Denosumab is combined with Floxuridine.
FludarabineThe risk or severity of adverse effects can be increased when Denosumab is combined with Fludarabine.
FludrocortisoneThe risk or severity of adverse effects can be increased when Denosumab is combined with Fludrocortisone.
FluorouracilThe risk or severity of adverse effects can be increased when Denosumab is combined with Fluorouracil.
GemcitabineThe risk or severity of adverse effects can be increased when Denosumab is combined with Gemcitabine.
Gemtuzumab ozogamicinThe risk or severity of adverse effects can be increased when Denosumab is combined with Gemtuzumab ozogamicin.
Glatiramer AcetateThe risk or severity of adverse effects can be increased when Denosumab is combined with Glatiramer Acetate.
golimumabThe risk or severity of adverse effects can be increased when Denosumab is combined with golimumab.
HydrocortisoneThe risk or severity of adverse effects can be increased when Denosumab is combined with Hydrocortisone.
HydroxyureaThe risk or severity of adverse effects can be increased when Denosumab is combined with Hydroxyurea.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Denosumab is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Ibrutinib.
IdarubicinThe risk or severity of adverse effects can be increased when Denosumab is combined with Idarubicin.
IdelalisibThe risk or severity of adverse effects can be increased when Denosumab is combined with Idelalisib.
IfosfamideThe risk or severity of adverse effects can be increased when Denosumab is combined with Ifosfamide.
ImatinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Imatinib.
ImiquimodThe risk or severity of adverse effects can be increased when Denosumab is combined with Imiquimod.
InfliximabThe risk or severity of adverse effects can be increased when Denosumab is combined with Infliximab.
IrinotecanThe risk or severity of adverse effects can be increased when Denosumab is combined with Irinotecan.
L-PhenylalanineThe risk or severity of adverse effects can be increased when Denosumab is combined with L-Phenylalanine.
LeflunomideThe risk or severity of adverse effects can be increased when Denosumab is combined with Leflunomide.
LenalidomideThe risk or severity of adverse effects can be increased when Denosumab is combined with Lenalidomide.
LomustineThe risk or severity of adverse effects can be increased when Denosumab is combined with Lomustine.
MechlorethamineThe risk or severity of adverse effects can be increased when Denosumab is combined with Mechlorethamine.
MelphalanThe risk or severity of adverse effects can be increased when Denosumab is combined with Melphalan.
MercaptopurineThe risk or severity of adverse effects can be increased when Denosumab is combined with Mercaptopurine.
MethotrexateThe risk or severity of adverse effects can be increased when Denosumab is combined with Methotrexate.
MethylprednisoloneThe risk or severity of adverse effects can be increased when Denosumab is combined with Methylprednisolone.
MitomycinThe risk or severity of adverse effects can be increased when Denosumab is combined with Mitomycin.
MitoxantroneThe risk or severity of adverse effects can be increased when Denosumab is combined with Mitoxantrone.
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Denosumab is combined with Mycophenolate mofetil.
Mycophenolic acidThe risk or severity of adverse effects can be increased when Denosumab is combined with Mycophenolic acid.
NatalizumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Natalizumab.
NelarabineThe risk or severity of adverse effects can be increased when Denosumab is combined with Nelarabine.
NilotinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Nilotinib.
ObinutuzumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Obinutuzumab.
OsimertinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Osimertinib.
OxaliplatinThe risk or severity of adverse effects can be increased when Denosumab is combined with Oxaliplatin.
PaclitaxelThe risk or severity of adverse effects can be increased when Denosumab is combined with Paclitaxel.
PalbociclibThe risk or severity of adverse effects can be increased when Denosumab is combined with Palbociclib.
PanobinostatThe risk or severity of adverse effects can be increased when Denosumab is combined with Panobinostat.
PazopanibThe risk or severity of adverse effects can be increased when Denosumab is combined with Pazopanib.
PegaspargaseThe risk or severity of adverse effects can be increased when Denosumab is combined with Pegaspargase.
PemetrexedThe risk or severity of adverse effects can be increased when Denosumab is combined with Pemetrexed.
PentostatinThe risk or severity of adverse effects can be increased when Denosumab is combined with Pentostatin.
PomalidomideThe risk or severity of adverse effects can be increased when Denosumab is combined with Pomalidomide.
PralatrexateThe risk or severity of adverse effects can be increased when Denosumab is combined with Pralatrexate.
PrednisoloneThe risk or severity of adverse effects can be increased when Denosumab is combined with Prednisolone.
PrednisoneThe risk or severity of adverse effects can be increased when Denosumab is combined with Prednisone.
ProcarbazineThe risk or severity of adverse effects can be increased when Denosumab is combined with Procarbazine.
Repository corticotropinThe risk or severity of adverse effects can be increased when Denosumab is combined with Repository corticotropin.
RilonaceptThe risk or severity of adverse effects can be increased when Denosumab is combined with Rilonacept.
RituximabThe risk or severity of adverse effects can be increased when Denosumab is combined with Rituximab.
RuxolitinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Ruxolitinib.
SecukinumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Secukinumab.
SiltuximabThe risk or severity of adverse effects can be increased when Denosumab is combined with Siltuximab.
SirolimusThe risk or severity of adverse effects can be increased when Denosumab is combined with Sirolimus.
SorafenibThe risk or severity of adverse effects can be increased when Denosumab is combined with Sorafenib.
StreptozocinThe risk or severity of adverse effects can be increased when Denosumab is combined with Streptozocin.
SunitinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Sunitinib.
TacrolimusThe risk or severity of adverse effects can be increased when Denosumab is combined with Tacrolimus.
TemozolomideThe risk or severity of adverse effects can be increased when Denosumab is combined with Temozolomide.
TemsirolimusThe risk or severity of adverse effects can be increased when Denosumab is combined with Temsirolimus.
TeniposideThe risk or severity of adverse effects can be increased when Denosumab is combined with Teniposide.
TeriflunomideThe risk or severity of adverse effects can be increased when Denosumab is combined with Teriflunomide.
ThalidomideThe risk or severity of adverse effects can be increased when Denosumab is combined with Thalidomide.
ThiotepaThe risk or severity of adverse effects can be increased when Denosumab is combined with Thiotepa.
TioguanineThe risk or severity of adverse effects can be increased when Denosumab is combined with Tioguanine.
TocilizumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Tocilizumab.
TofacitinibThe risk or severity of adverse effects can be increased when Denosumab is combined with Tofacitinib.
TopotecanThe risk or severity of adverse effects can be increased when Denosumab is combined with Topotecan.
TositumomabThe risk or severity of adverse effects can be increased when Denosumab is combined with Tositumomab.
TrabectedinThe risk or severity of adverse effects can be increased when Denosumab is combined with Trabectedin.
TretinoinThe risk or severity of adverse effects can be increased when Denosumab is combined with Tretinoin.
TriamcinoloneThe risk or severity of adverse effects can be increased when Denosumab is combined with Triamcinolone.
UstekinumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Ustekinumab.
VedolizumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Vedolizumab.
VinblastineThe risk or severity of adverse effects can be increased when Denosumab is combined with Vinblastine.
VincristineThe risk or severity of adverse effects can be increased when Denosumab is combined with Vincristine.
VindesineThe risk or severity of adverse effects can be increased when Denosumab is combined with Vindesine.
VinorelbineThe risk or severity of adverse effects can be increased when Denosumab is combined with Vinorelbine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced b...
Gene Name:
TNFSF11
Uniprot ID:
O14788
Molecular Weight:
35477.81 Da
References
  1. 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. [PubMed:18685421 ]
  2. 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. [PubMed:16702197 ]
Comments
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Drug created on March 19, 2008 10:43 / Updated on March 14, 2016 10:04