744262-65-5Relevant academic research and scientific papers
2-sulfinyl benzothiazoles, -oxazoles and -imidazoles are novel in vitro bone anti-reabsorptive compounds
Corbett,Kerr,Wong,Harlow,Boswell,Pease,Lee,Holliday,Gluck
, p. 151 - 167 (2007/10/03)
Bone resorption by osteoclasts is dependent on H+ transport into the external resorption lacunae, generating an acidic microenvironment in which bone mineral dissolution and matrix degradation occur. A vacuolar H+-ATPase is responsible for osteoclast H+ secretion. Here, we describe novel vacuolar H+-ATPase inhibitors that inhibit bone resorption in vitro. Several agents inhibited 45Ca release from mouse calvariae, 3H-proline release from bone particles by chicken osteoclast-like cells, and resorption pit formation by murine osteoclasts on dentine slices. One compound, a 2-sulfinylbenzothiazole (XS238), is significantly more potent than previously reported vacuolar H+-ATPase inhibitors, exhibiting an IC50 of 5 μM in the 45Ca release assay, an IC50 of 1 μM in the 3H-proline release assay, and an IC50 of 100 nM in the resorption pit assay. The potent H+-ATPase inhibitors described may have value in treating osteoporosis and other bone diseases.
