Reference

Nitrogen-containing bisphosphonates induce S-phase cell cycle arrest and apoptosis of myeloma cells by activating MAPK pathway and inhibiting mevalonate pathway

Nitrogen-containing bisphosphonates induce S-phase cell cycle arrest and apoptosis of myeloma cells by activating MAPK pathway and inhibiting mevalonate pathway. Iguchi, Toyotaka; Miyakawa, Yoshitaka; Yamamoto, Kaori; Kizaki, Masahiro; Ikeda, Yasuo (Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan). Cellular Signalling, 15(7), 719-727 (English) 2003 Elsevier Science Inc. CODEN: CESIEY. ISSN: 0898-6568. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Bisphosphonates have been used for the treatment of hypercalcemia assocd. with malignancies and osteoporosis. It was previously reported that the mevalonate pathway is involved in nitrogen-contg. bisphosphonate-induced apoptosis in osteoclasts and myeloma cells. The aim of this study was to det. the effects of two bisphosphonates, incadronate, and newly developed bisphosphonate YM529 on human myeloma cells, U266, RPMI-8226, and HS-Sultan. Both incadronate and YM529 induced S-phase cell cycle arrest and apoptosis in these myeloma cells. 138330-18-4 and 13598-36-2 which are cas registry numbers of chemicals are mentioned. Treatment of the myeloma cells with cell-permeable substrates for mevalonate pathways, geranylgeraniol, and farnesol prevented bisphosphonate-mediated growth suppression. Checkpoint kinases, Chk1/2, and MAPK became phosphorylated after stimulation with bisphosphonates in the myeloma cells. Bisphosphonate-induced apoptosis was partially prevented by the pretreatment with MAPK inhibitor. These results demonstrate that incadronate and YM529 suppress the proliferation of myeloma cells through mevalonate pathway and MAPK pathway. .

Bisphosphonate resinates

All Rights Reserved. Bisphosphonate resinates. Stockel, Richard F.; Budnick, Edward G. (USA ). U.S. Pat. Appl. Publ. US 2007003512 A1 4 Jan 2007,6pp. (English). (United States of America). CODEN: USXXCO. INCL: 424076100; 514089000; 514102000. APPLICATION: US 2005-156513 20 Jun 2005. DOCUMENT TYPE: Patent CA Section: 63 (Pharmaceuticals) The present invention is directed to novel and new oral parenteral compns. comprising various bisphosphonates in conjunction with bound or unbound ion exchange resins, or mixts. of the two types of resins thereof. Accordingly, the said dosage forms effect the delivery to the lower intestinal tract in humans or animals prohibiting the exposure of the bisphosphonates to the epithelial and mucosal tissues of the buccal cavity, pharynx, esophagus, and stomach. These drug-resinates also have the systemic effect of providing a slow release mechanism, thereby extending the efficacy of the treatment for a longer period of time. The drug resinates can also incorporate ionic charged bioactive mols. contg. 9004-34-6 and 138330-18-4 are just another two chemicals used in this study. carboxylate, amino or pos. charged amino groups having synergistic value in conjunction with bisphosphonates. .