denosumab   

GtoPdb Ligand ID: 6886

Synonyms: AMG-162 | M05BX04 | Prolia® | Xgeva®
denosumab is an approved drug (FDA and EMA (2010))
Compound class: Antibody
Comment: Denosumab suppresses the activity of RANK ligand (RANKL), which normally promotes bone removal and resorption, but which becomes over active in many bone loss diseases.
Denosumab is produced from CHO cells stably expressing recombinant antibody component proteins [1].
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Summary of Clinical Use
Prolia® (FDA approval 2010) is used to treat bone loss in postmenopausal osteoporosis, men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. In May 2018 the FDA approval for Prolia® was expanded to include treatment of glucocorticoid-induced osteoporosis in males and females who are at high risk of fracture.
Xgeva® (FDA approval 2011) is used for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In December 2014 Xgeva® approval was expanded to include treatment of hypercalcemia of malignancy (HCM) whch is refractory to traditional bisphosphonate therapy. HCM can develop in cancer patients, with symptoms arising from cancer-driven increases in bone resorption. Untreated HCM can lead to renal failure, progressive mental impairment, coma and death [2,4].
Mechanism Of Action and Pharmacodynamic Effects
Denosumab is a high-affinity, selective inhibitor of receptor activator of nuclear factor-kappaB ligand (RANKL). Inhibition of RANKL-mediated RANK activation on pre-osteoclasts reduces their maturation to osteoclasts, thus protecting bone from degradation [3] and shifting the equilibrium of bone re-modelling towards bone formation.
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