| Attributes | Values |
|---|
| rdf:type
| |
| http://linked.open...gbank/description
| - 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] (en)
|
| http://linked.open...generalReferences
| - 1. Iguchi, Toyotaka, et al. "Nitrogen-containing bisphosphonates induce S-phase cell cycle arrest and apoptosis of myeloma cells by activating MAPK pathway and inhibiting mevalonate pathway." Cellular signalling 15.7 (2003): 719-727. 2. Ishikawa, Chie, et al. "Bisphosphonate incadronate inhibits growth of human T‐cell leukaemia virus type I‐infected T‐cell lines and primary adult T‐cell leukaemia cells by interfering with the mevalonate pathway." British journal of haematology 136.3 (2007): 424-432. 3. Kim, Sung-Bae, et al. "Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study." Current therapeutic research 68.3 (2007): 193-204. 4. Matsuo, Atsushi, et al. "Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis." The Journal of rheumatology 30.6 (2003): 1280-1290. 5. Oades, Grenville M., et al. "Nitrogen containing bisphosphonates induce apoptosis and inhibit the mevalonate pathway, impairing Ras membrane localization in prostate cancer cells." The Journal of urology 170.1 (2003): 246-252. 6. Ochiai, Yamada, et al. Nitrogen-containing bisphosphonate incadronate augments the inhibitory effect of farnesyl transferase inhibitor tipifarnib on the growth of fresh and cloned myeloma cells in vitro Leuk Lymphoma, 46 (11) (2005), pp. 1619–1625 7. Shipman, Claire M., et al. "The bisphosphonate incadronate (YM175) causes apoptosis of human myeloma cells in vitro by inhibiting the mevalonate pathway." Cancer Research 58.23 (1998): 5294-5297. 8. Usui, T., et al. "Pharmacokinetics of incadronate, a new bisphosphonate, in healthy volunteers and patients with malignancy-associated hypercalcemia." International journal of clinical pharmacology and therapeutics 35.6 (1997): 239-244. (en)
|
| http://linked.open...gy/drugbank/group
| - approved (en)
- investigational (en)
|
| http://linked.open...drugbank/halfLife
| - 0.26-0.40 h (t1/2 alpha) and 1.58 - 1.98 h (t1/2 beta). [8] (en)
|
| http://linked.open...ugbank/indication
| - For the treatment of hypercalcemia associated with malignant disease. (en)
|
| sameAs
| |
| Title
| |
| adms:identifier
| |
| http://linked.open...mechanismOfAction
| - 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] (en)
|
| http://linked.open...outeOfElimination
| - Renally eliminated. [8] (en)
|
| http://linked.open.../drugbank/synonym
| - Cimadronate (en)
- Incadronic acid (en)
- YM-175 (en)
|
| http://linked.open...umeOfDistribution
| - 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] (en)
|
| http://linked.open...ogy/drugbank/salt
| |
| http://linked.open...ugbank/IUPAC-Name
| |
| http://linked.open...gy/drugbank/InChI
| |
| http://linked.open...Molecular-Formula
| |
| http://linked.open.../Molecular-Weight
| |
| http://linked.open...noisotopic-Weight
| |
| http://linked.open...y/drugbank/SMILES
| |
| http://linked.open.../Water-Solubility
| |
| http://linked.open...ogy/drugbank/logP
| |
| http://linked.open...ogy/drugbank/logS
| |
| http://linked.open...nd-Acceptor-Count
| |
| http://linked.open...-Bond-Donor-Count
| |
| http://linked.open...drugbank/InChIKey
| |
| http://linked.open...urface-Area--PSA-
| |
| http://linked.open...nk/Polarizability
| |
| http://linked.open...bank/Refractivity
| |
| http://linked.open...atable-Bond-Count
| |
| http://linked.open...ugbank/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] (en)
|
| http://linked.open.../affectedOrganism
| - Humans and other mammals (en)
|
| http://linked.open...casRegistryNumber
| |
| http://linked.open...drugbank/category
| |
| http://linked.open...rugbank/clearance
| - 60% renal clearance. [8] Changes in renal clearance may affect the pharmacokinetics of incadronate. (en)
|
| http://linked.open...k/Bioavailability
| |
| http://linked.open...bank/Ghose-Filter
| |
| http://linked.open...nk/MDDR-Like-Rule
| |
| http://linked.open...k/Number-of-Rings
| |
| http://linked.open...siological-Charge
| |
| http://linked.open...bank/Rule-of-Five
| |
| http://linked.open...tional-IUPAC-Name
| |
| http://linked.open...strongest-acidic-
| |
| http://linked.open...-strongest-basic-
| |
![[RDF Data]](/fct/images/sw-rdf-blue.png)
![[cxml]](/fct/images/cxml_doc.png)
![[csv]](/fct/images/csv_doc.png)
![[text]](/fct/images/ntriples_doc.png)
![[turtle]](/fct/images/n3turtle_doc.png)
![[ld+json]](/fct/images/jsonld_doc.png)
![[rdf+json]](/fct/images/json_doc.png)
![[rdf+xml]](/fct/images/xml_doc.png)
![[atom+xml]](/fct/images/atom_doc.png)
![[html]](/fct/images/html_doc.png)