Detailed description page of THPdb

Details of Th1123 which contains 6 entries.

Entry 1
(1) Primary information
ID 1570
ThPP ID Th1123
Therapeutic Peptide/Protein Name Denosumab
Sequence Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification IIIc
Molecular Weight 144700
Chemical Formula C6404H9912N1724O2004S50
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life 25.4 days
Description Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease 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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism N.A.
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 N.A.
Clearance N.A.
Categories Bone Density Conservation Agents and Monoclonal antibodies
Patents Number CA2257247
Date of Issue 12/09/16
Date of Expiry 16/04/22
Drug Interaction N.A.
Target Tumor necrosis factor ligand superfamily member 11
Information of corresponding available drug in the market
Brand Name Xgeva
Company Amgen.
Brand Discription Xgeva (denosumab) is a human IgG2 monoclonal antibody that binds to human RANKL. Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells.
Prescribed for Bone Metastasis From Solid Tumors, Giant Cell Tumor Of Bone, Hypercalcemia Of Malignancy
Chemical Name N.A.
Formulation Each single-use vial of Xgeva contains 120 mg denosumab, acetate (18 mM), sorbitol (4.6%), Water for Injection (USP), and sodium hydroxide to a pH of 5.2
Physcial Appearance Sterile, preservative-free, clear, colorless to pale yellow solution
Route of Administration N.A.
Recommended Dosage Bone Metastasis From Solid Tumors: The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.; Giant Cell Tumor Of Bone: The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.; Hypercalcemia Of Malignancy: The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy.
Contraindication Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
Side Effects Hypocalcemia, Osteonecrosis of the Jaw.
Useful Link http://www.rxlist.com/xgeva-drug.htm http://www.xgeva.com/ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm234346.htm
PubMed ID 23159111, 16872263
3-D Structure Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

Entry 2
(2) Primary information
ID 1571
ThPP ID Th1123
Therapeutic Peptide/Protein Name Denosumab
Sequence Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification IIIc
Molecular Weight 144700
Chemical Formula C6404H9912N1724O2004S50
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life 25.4 days
Description Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease 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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism N.A.
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 N.A.
Clearance N.A.
Categories Bone Density Conservation Agents and Monoclonal antibodies
Patents Number CA2274987
Date of Issue 25/01/16
Date of Expiry 23/12/21
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name Prolia
Company Amgen.
Brand Discription Prolia (denosumab) is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of nuclear factor kappa-B ligand). Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells.
Prescribed for Treatment Of Postmenopausal Women With Osteoporosis At High Risk For Fracture,Treatment To Increase Bone Mass In Men With Osteoporosis, Treatment Of Bone Loss In Men Receiving Androgen Deprivation Therapy For Prostate Cancer, Treatment Of Bone Loss In Women Receiving Adjuvant Aromatase Inhibitor Therapy For Breast Cancer
Chemical Name N.A.
Formulation Each 1 mL single-use prefilled syringe of Prolia contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, 0.01% polysorbate 20, Water for Injection (USP), and sodium hydroxide to a pH of 5.2. Each 1 mL single-use vial of Prolia contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, Water for Injection (USP), and sodium hydroxide to a pH of 5.2
Physcial Appearance Sterile, preservative-free, clear, colorless to pale yellow solution
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication Hypocalcemia. Pregnancy. Hypersensitivity
Side Effects Hypocalcemia, Serious Infections, Dermatologic Adverse Reactions, Osteonecrosis of the Jaw, Atypical Subtrochanteric and Diaphyseal Femoral Fractures
Useful Link http://www.rxlist.com/prolia-drug.htm drugs.com/prolia-html http://www.prolia.com/
PubMed ID 23159111, 16872263
3-D Structure Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

Entry 3
(3) Primary information
ID 1572
ThPP ID Th1123
Therapeutic Peptide/Protein Name Denosumab
Sequence Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification IIIc
Molecular Weight 144700
Chemical Formula C6404H9912N1724O2004S50
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life 25.4 days
Description Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease 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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism N.A.
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 N.A.
Clearance N.A.
Categories Bone Density Conservation Agents and Monoclonal antibodies
Patents Number CA2285746
Date of Issue 29/09/14
Date of Expiry 16/04/22
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 23159111, 16872263
3-D Structure Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

Entry 4
(4) Primary information
ID 1573
ThPP ID Th1123
Therapeutic Peptide/Protein Name Denosumab
Sequence Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification IIIc
Molecular Weight 144700
Chemical Formula C6404H9912N1724O2004S50
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life 25.4 days
Description Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease 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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism N.A.
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 N.A.
Clearance N.A.
Categories Bone Density Conservation Agents and Monoclonal antibodies
Patents Number CA2400929
Date of Issue 01/06/15
Date of Expiry 24/02/25
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 23159111, 16872263
3-D Structure Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

Entry 5
(5) Primary information
ID 1574
ThPP ID Th1123
Therapeutic Peptide/Protein Name Denosumab
Sequence Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification IIIc
Molecular Weight 144700
Chemical Formula C6404H9912N1724O2004S50
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life 25.4 days
Description Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease 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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism N.A.
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 N.A.
Clearance N.A.
Categories Bone Density Conservation Agents and Monoclonal antibodies
Patents Number CA2328140
Date of Issue 14/03/16
Date of Expiry 14/05/23
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 23159111, 16872263
3-D Structure Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

Entry 6
(6) Primary information
ID 1575
ThPP ID Th1123
Therapeutic Peptide/Protein Name Denosumab
Sequence Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification IIIc
Molecular Weight 144700
Chemical Formula C6404H9912N1724O2004S50
Isoelectric Point N.A.
Hydrophobicity N.A.
Melting Point (℃) N.A.
Half Life 25.4 days
Description Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease 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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism N.A.
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 N.A.
Clearance N.A.
Categories Bone Density Conservation Agents and Monoclonal antibodies
Patents Number N.A.
Date of Issue N.A.
Date of Expiry N.A.
Drug Interaction N.A.
Target N.A.
Information of corresponding available drug in the market
Brand Name N.A.
Company N.A.
Brand Discription N.A.
Prescribed for N.A.
Chemical Name N.A.
Formulation N.A.
Physcial Appearance N.A.
Route of Administration N.A.
Recommended Dosage N.A.
Contraindication N.A.
Side Effects N.A.
Useful Link N.A.
PubMed ID 23159111, 16872263
3-D Structure Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

OSDDlinux

Raghava's Group

IMTECH

CSIR

CRDD
CPPSITE 2.0

(1) Primary information
Entry 1
ID	1570
ThPP ID	Th1123
Therapeutic Peptide/Protein Name	Denosumab
Sequence	Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification	IIIc
Molecular Weight	144700
Chemical Formula	C6404H9912N1724O2004S50
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	25.4 days
Description	Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease	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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism	N.A.
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	N.A.
Clearance	N.A.
Categories	Bone Density Conservation Agents and Monoclonal antibodies
Patents Number	CA2257247
Date of Issue	12/09/16
Date of Expiry	16/04/22
Drug Interaction	N.A.
Target	Tumor necrosis factor ligand superfamily member 11
Information of corresponding available drug in the market
Brand Name	Xgeva
Company	Amgen.
Brand Discription	Xgeva (denosumab) is a human IgG2 monoclonal antibody that binds to human RANKL. Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells.
Prescribed for	Bone Metastasis From Solid Tumors, Giant Cell Tumor Of Bone, Hypercalcemia Of Malignancy
Chemical Name	N.A.
Formulation	Each single-use vial of Xgeva contains 120 mg denosumab, acetate (18 mM), sorbitol (4.6%), Water for Injection (USP), and sodium hydroxide to a pH of 5.2
Physcial Appearance	Sterile, preservative-free, clear, colorless to pale yellow solution
Route of Administration	N.A.
Recommended Dosage	Bone Metastasis From Solid Tumors: The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.; Giant Cell Tumor Of Bone: The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.; Hypercalcemia Of Malignancy: The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy.
Contraindication	Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
Side Effects	Hypocalcemia, Osteonecrosis of the Jaw.
Useful Link	http://www.rxlist.com/xgeva-drug.htm http://www.xgeva.com/ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm234346.htm
PubMed ID	23159111, 16872263
3-D Structure	Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

(2) Primary information
Entry 2
ID	1571
ThPP ID	Th1123
Therapeutic Peptide/Protein Name	Denosumab
Sequence	Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification	IIIc
Molecular Weight	144700
Chemical Formula	C6404H9912N1724O2004S50
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	25.4 days
Description	Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease	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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism	N.A.
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	N.A.
Clearance	N.A.
Categories	Bone Density Conservation Agents and Monoclonal antibodies
Patents Number	CA2274987
Date of Issue	25/01/16
Date of Expiry	23/12/21
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	Prolia
Company	Amgen.
Brand Discription	Prolia (denosumab) is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of nuclear factor kappa-B ligand). Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells.
Prescribed for	Treatment Of Postmenopausal Women With Osteoporosis At High Risk For Fracture,Treatment To Increase Bone Mass In Men With Osteoporosis, Treatment Of Bone Loss In Men Receiving Androgen Deprivation Therapy For Prostate Cancer, Treatment Of Bone Loss In Women Receiving Adjuvant Aromatase Inhibitor Therapy For Breast Cancer
Chemical Name	N.A.
Formulation	Each 1 mL single-use prefilled syringe of Prolia contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, 0.01% polysorbate 20, Water for Injection (USP), and sodium hydroxide to a pH of 5.2. Each 1 mL single-use vial of Prolia contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, Water for Injection (USP), and sodium hydroxide to a pH of 5.2
Physcial Appearance	Sterile, preservative-free, clear, colorless to pale yellow solution
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	Hypocalcemia. Pregnancy. Hypersensitivity
Side Effects	Hypocalcemia, Serious Infections, Dermatologic Adverse Reactions, Osteonecrosis of the Jaw, Atypical Subtrochanteric and Diaphyseal Femoral Fractures
Useful Link	http://www.rxlist.com/prolia-drug.htm drugs.com/prolia-html http://www.prolia.com/
PubMed ID	23159111, 16872263
3-D Structure	Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

(3) Primary information
Entry 3
ID	1572
ThPP ID	Th1123
Therapeutic Peptide/Protein Name	Denosumab
Sequence	Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification	IIIc
Molecular Weight	144700
Chemical Formula	C6404H9912N1724O2004S50
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	25.4 days
Description	Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease	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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism	N.A.
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	N.A.
Clearance	N.A.
Categories	Bone Density Conservation Agents and Monoclonal antibodies
Patents Number	CA2285746
Date of Issue	29/09/14
Date of Expiry	16/04/22
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	23159111, 16872263
3-D Structure	Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

(4) Primary information
Entry 4
ID	1573
ThPP ID	Th1123
Therapeutic Peptide/Protein Name	Denosumab
Sequence	Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification	IIIc
Molecular Weight	144700
Chemical Formula	C6404H9912N1724O2004S50
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	25.4 days
Description	Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease	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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism	N.A.
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	N.A.
Clearance	N.A.
Categories	Bone Density Conservation Agents and Monoclonal antibodies
Patents Number	CA2400929
Date of Issue	01/06/15
Date of Expiry	24/02/25
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	23159111, 16872263
3-D Structure	Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

(5) Primary information
Entry 5
ID	1574
ThPP ID	Th1123
Therapeutic Peptide/Protein Name	Denosumab
Sequence	Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification	IIIc
Molecular Weight	144700
Chemical Formula	C6404H9912N1724O2004S50
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	25.4 days
Description	Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease	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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism	N.A.
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	N.A.
Clearance	N.A.
Categories	Bone Density Conservation Agents and Monoclonal antibodies
Patents Number	CA2328140
Date of Issue	14/03/16
Date of Expiry	14/05/23
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	23159111, 16872263
3-D Structure	Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)

(6) Primary information
Entry 6
ID	1575
ThPP ID	Th1123
Therapeutic Peptide/Protein Name	Denosumab
Sequence	Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVR view full sequnce in fasta
Functional Classification	IIIc
Molecular Weight	144700
Chemical Formula	C6404H9912N1724O2004S50
Isoelectric Point	N.A.
Hydrophobicity	N.A.
Melting Point (℃)	N.A.
Half Life	25.4 days
Description	Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010.
Indication/Disease	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.
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.
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 (â‰¥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials
Metabolism	N.A.
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	N.A.
Clearance	N.A.
Categories	Bone Density Conservation Agents and Monoclonal antibodies
Patents Number	N.A.
Date of Issue	N.A.
Date of Expiry	N.A.
Drug Interaction	N.A.
Target	N.A.
Information of corresponding available drug in the market
Brand Name	N.A.
Company	N.A.
Brand Discription	N.A.
Prescribed for	N.A.
Chemical Name	N.A.
Formulation	N.A.
Physcial Appearance	N.A.
Route of Administration	N.A.
Recommended Dosage	N.A.
Contraindication	N.A.
Side Effects	N.A.
Useful Link	N.A.
PubMed ID	23159111, 16872263
3-D Structure	Th1123 Heavy chainor (Download)Th1123 Light chain (View) or (Download)