Incadronic acid
未知生产厂商
Incadronate, or YM-175, is a nitrogen containing bisphosphonate. Along with being investigated to treat hypercalcemia of malignancy, it has also been investigated in the treatment of myeloma, leukemia, and other cancers. Incadronic acid was first described in the literature in 1991.
Incadronate, or YM-175, is a nitrogen containing bisphosphonate. Along with being investigated to treat hypercalcemia of malignancy, it has also been investigated in the treatment of myeloma, leukemia, and other cancers. Incadronic acid was first described in the literature in 1991.
Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. Nitrogen containing bisphosphonates such as incandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. incadronate also activated caspases 3, 4, and 7; further contributing to apoptosis.
Incadronate has been investigated in the treatment of myeloma, leukemia, and other cancers. It has also been investigated in patients with hypercalcemia of malignancy.
