Tìm theo
Incadronate
Các tên gọi khác (3) :
  • Cimadronate
  • Incadronic acid
  • YM-175
bone density conservation agents
Thuốc Gốc
Small Molecule
CAS: 138330-18-4
CTHH: C7H17NO6P2
PTK: 273.1605
Incadronic acid is a third generation bisphosphonate which can suppress bone resorption by osteoclasts. It is used to treat hypercalcemia, and bone disorders associated with malignancy and osteoporosis. In rats with induced hypercalcemia, incadronate has been found to be 46 times more potent than pamidronate and 11 times more potent than aledronate. Incadronate has also been found to have anti-tumor effects in mice. In rat models of breast cancer, bisphosphonate treatment has been shown to inhibit the progression and development of bone metastases and reduce tumor burden in vivo. It has also been recognized as a potential treatment for adult T-cell leukaemia which is characterized by hypercalcemia and tumor-induced osteolysis. [4] Incadronate, as well as other nitrogen containing bisphosphonates, such as aledronate and minodronate, have been found to induce apoptosis of hematopoietic tumor cells. In vitro human myeloma cells have undergone apoptosis when exposed to incadronate. [7] When combined with Tipifarnib, a potent farnesyl transferase inhibitor which can suppress the growth of myeloma cells, growth suppression of myeloma cells in vitro is intensified. [6] Because of these findings Incadronate is being investigated as a treatment for multiple myeloma, a B-cell malignancy associated with bone loss. Incadronate is available by prescription only, and is not marked is the United States, UK, Canada, or Australia. [Wikipedia] It is an approved treatment for malignancy-associated hypercalcemia (MAH) in Japan.[3]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C7H17NO6P2
Phân tử khối
273.1605
Monoisotopic mass
273.053110305
InChI
InChI=1S/C7H17NO6P2/c9-15(10,11)7(16(12,13)14)8-6-4-2-1-3-5-6/h6-8H,1-5H2,(H2,9,10,11)(H2,12,13,14)
InChI Key
InChIKey=GBBBPWVJGMFZGX-UHFFFAOYSA-N
IUPAC Name
[(cyclohexylamino)(phosphono)methyl]phosphonic acid
Traditional IUPAC Name
(cyclohexylamino)(phosphono)methylphosphonic acid
SMILES
OP(O)(=O)C(NC1CCCCC1)P(O)(O)=O
Độ hòa tan
1.44e+01 g/l
logP
-1.8
logS
-1.3
pKa (strongest acidic)
-1.1
pKa (Strongest Basic)
5.48
PSA
127.09 Å2
Refractivity
57.17 m3·mol-1
Polarizability
23.53 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
7
H Bond Donor Count
5
Physiological Charge
-2
Number of Rings
1
Bioavailability
1
Rule of Five
true
Cơ Chế Tác Dụng : Incadronic acid is a third generation bisphosphonate which can suppress bone resorption by osteoclasts. It is used to treat hypercalcemia, and bone disorders associated with malignancy and osteoporosis. In rats with induced hypercalcemia, incadronate has been found to be 46 times more potent than pamidronate and 11 times more potent than aledronate. Incadronate has also been found to have anti-tumor effects in mice. In rat models of breast cancer, bisphosphonate treatment has been shown to inhibit the progression and development of bone metastases and reduce tumor burden in vivo. It has also been recognized as a potential treatment for adult T-cell leukaemia which is characterized by hypercalcemia and tumor-induced osteolysis. [4] Incadronate, as well as other nitrogen containing bisphosphonates, such as aledronate and minodronate, have been found to induce apoptosis of hematopoietic tumor cells. In vitro human myeloma cells have undergone apoptosis when exposed to incadronate. [7] When combined with Tipifarnib, a potent farnesyl transferase inhibitor which can suppress the growth of myeloma cells, growth suppression of myeloma cells in vitro is intensified. [6] Because of these findings Incadronate is being investigated as a treatment for multiple myeloma, a B-cell malignancy associated with bone loss. Incadronate is available by prescription only, and is not marked is the United States, UK, Canada, or Australia. [Wikipedia] It is an approved treatment for malignancy-associated hypercalcemia (MAH) in Japan.[3] Incadronate suppresses bone resorption by inhibiting osteoclasts. Incadronate was found to induce apoptosis in myeloma cells by S-phase cell cycle arrest via inhibition of the mevalonate (MVA) pathway and activation of the MAPK pathway. [1] Similarly, in studies looking at the potential role of incadronate as a treatment for adult T-cell leukemia, incadronate has been shown to inhibit the growth of T-cell lines infected with the human T-cell leukaemia virus by inducing apoptosis and S-phase cell cycle arrest by inhibiting the mevalonate pathway. Nitrogen containing bisphosphonates such as incandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the Ras signaling pathway, as well as activating the Bim-mediated mitochondrial intrinsic apoptotic pathway. [5] They also induce apoptosis by inhibiting the prenylation of small G-proteins. [5]
Dược Động Học :
▧ Absorption :
Pharmacokinetic studies in patients with MAH have indicated linear pharmacokinetics with intravenous administration. [8] In studies comparing absorption of incadronate in healthy volunteers verses volunteers with MAH plasma levels have been similar at 2 h, however at 8 h the plasma levels are three times higher in patients with MAH. This can be explained by the decrease in renal function experienced by patients with MAH. Notably, however, the plasma levels of incadronate are not as high as expected based on the reduction in renal clearance. This indicates that patients with hypercalcemia may experience enhanced bone uptake of the drug. [8]
▧ Volume of Distribution :
Incadronate rapidly relocalizes to bone due to its high affinity for mineralized bone. [4] Due to its incorporation into bone marrow osteoclasts the concentration of incadronate in the bone marrow is high. [4]
▧ Route of Elimination :
Renally eliminated. [8]
▧ Half Life :
0.26-0.40 h (t1/2 alpha) and 1.58 - 1.98 h (t1/2 beta). [8]
▧ Clearance :
60% renal clearance. [8] Changes in renal clearance may affect the pharmacokinetics of incadronate.
Chỉ Định : For the treatment of hypercalcemia associated with malignant disease.
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06255
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07123
Wikipedia
http://en.wikipedia.org/wiki/Incadronic_acid
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