Denosumab CAS 615258-40-7

Introduction：Basic information about Denosumab CAS 615258-40-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Denosumab Basic information

• Product Name: Denosumab
• Synonyms: D03684;Denosumab;Denosumab (usan);AMG 162;IMMunoglobulin G2, anti-(huMan osteoclast differentiation factor) (huMan Monoclonal AMG162 heavy chain), disulfide with huMan Monoclonal AMG162 light chain, diMer;Denosumab (usan) USP/EP/BP;Research Grade Denosumab (DHA30301);Denosumab,Immunoglobulin G2,Nuclear factor-kappaB,NF-κB,Immunoglobulin G-2,RANKL,Inhibitor,Ranmark,inhibit,Cancer,Immunoglobulin G 2,Osteoporosis,Nuclear factor-κB
• CAS: 615258-40-7
• MF: C6404H9912N1724O2004S50
• MW: 0
• Mol File: Mol File

Denosumab Chemical Properties

• form: Liquid
• color: Colorless to light yellow

Denosumab Usage And Synthesis

Description

Denosumab, which was approved in the United States in 2010, is a fullyhuman sequence IgG2 monoclonal antibody that inhibits bone resorptionby blocking the activity of receptor activator of nuclear factor-κB ligand(RANKL). RANKL is a TNF family protein that is expressed in bothsecreted and cell surface forms by a variety of bone marrow cell typesandmediates bone resorption through its receptor (RANK),which is foundon osteoclasts and osteoclast precursors . Denosumab was discoveredusing XenomouseTM transgenic mice comprising human immunoglobulingenes. The antibody is approved for treatment of postmenopausalwomen with osteoporosis at high risk for fracture, and for the prevention ofskeletal-related events in patients with bone metastases from solid tumors.Denosumab competes directly with bisphosphonates such as alendronicacid in postmenopausal osteoporosis and with zoledronic acid in both ofthese indications. It has been shown to have comparable efficacy and safetyto bisphosphonates with some tolerability and patient acceptability advantages.

Originator

Amgen (United States)

History

Denosumab was approved by the FDA approved on June 2010 for the treatment of osteoporosis in postmenopausal women. It further received additional indication approval to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer and women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer in September 2011 and in men with osteoporosis at high risk for fracture in September 2012.An Denosumab biosimilar, Jubbonti, was approved for Health Canada in February 2024. Two denosumab biosimilars—Wyost® (denosumab-bbdz) 11 and Jubbonti® (denosumab-bbdz)—were approved by the FDA in March 2024 for all indications of the reference products Xgeva® and Prolia®; Both biosimilars also received marketing authorization in the EU in May 2024.

Uses

Prevention and treatment of all forms of osteoporosis or bone loss.

Indications

1. Prevention of skeletal-related events (e.g., bone pain and fractures) secondary to multiple myeloma or bone metastases from solid tumors. Used in conjunction with treatments for primary malignancy.
2. Giant cell tumor of the bone. Indicated in adults and skeletally mature adolescents with an unresectable tumor or when surgical resection would likely cause severe morbidity.
3. Hypercalcemia of malignancy. This drug is indicated when hypercalcemia is refractory to bisphosphonate therapy.
4. Osteoporosis. Indicated as therapy for postmenopausal women with osteoporosis at high risk for fracture. Indications also include the treatment of men with osteoporosis at high risk of fracture. A high risk for fracture is defined as those with multiple risk factors for fracture, a known history of an osteoporotic fracture, or those who have failed prior osteoporosis treatment (e.g., bisphosphonates).
5. Glucocorticoid-induced osteoporosis. Indicated for treatment in patients of both sexes at high risk for fracture who are initiating or continuing systemic glucocorticoids at a dose greater than or equal to 7.5 mg of prednisone daily for an expected duration of at least six months.
6. Bone loss. Indicated for treating androgen deprivation-induced bone loss and aromatase inhibitor-induced bone loss. The goal of therapy is to increase bone mass in men with prostate cancer receiving androgen deprivation therapy. In women, the treatment goal is to increase bone mass when receiving aromatase inhibitor therapy for breast cancer.

Brand name

Prolia;Xgeva

Mechanism of action

Briefly, denosumab is a fully human monoclonal antibody that inhibits RANKL and helps regulate turnover in healthy bone. Denosumab binds with high specificity and affinity to the cytokine  RANKL, inhibiting its action; as a result, osteoclast recruitment,  maturation and action are inhibited, and bone resorption slows.

Clinical Use

Human monoclonal antibody (IgG2):
Osteoporosis in postmenopausal women and men with prostate cancer after hormone ablation at risk of fractures
Reduction of bone damage in patients with bone metastases from solid tumours

Side effects

• red, dry, or itchy skin
• oozing or crusty blisters on skin
• peeling skin
• back pain
• pain in your arms
• swelling of arms or legs
• muscle or joint pain
• nausea

Metabolism

Metabolism and elimination are expected to follow the immunoglobulin clearance pathways, resulting in degradation to small peptides and individual amino acids.