CAS: 143313-51-3; (4S,7S,10S,13S)-13-Formyl-4-(4-Hydroxybenzyl)-7-Isopropyl-10-Methyl-2,5,8,11-Tetraoxo-3,6,9,12-Tetraazapentadecan-15-Oic Acid

专利信息

专利号:US-8329686-B2
优先权日:2006-08-29
标题:Isatin analogues and uses therefor
发明人：MACH ROBERT H; WELCH MICHAEL; CHU WENHUA; ROTHFUSS JUSTIN
权利人:MACH ROBERT H; WELCH MICHAEL; CHU WENHUA; ROTHFUSS JUSTIN; UNIV WASHINGTON
摘要:Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vivo imaging of apoptosis by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

专利号:US-6699676-B1
优先权日:1999-06-03
标题:Uses of ouabain and ouabain-like molecules in apoptosis related pathologies
发明人：ORLOV SERGEI N; HAMET PAVEL; TREMBLAY JOHANNE
权利人:CORP DU CT DE RECH DU CT HOSPI
摘要:Longterm elevation of the intracellular Na + /K + ratio inhibits macromolecule synthesis and proliferation in the majority of cell types studied so far, including vascular smooth muscle cells (VSMC). We report here that inhibition of the Na + ,K + pump in VSMC by ouabain or 1 hour preincubation in K + -depleted medium attenuated apoptosis triggered by serum withdrawal, staurosporine or okadaic acid. In the absence of ouabain, both DNA degradation and caspase-3 activation in VSMC undergoing apoptosis were insensitive to modification of the extracellular Na + /K + ratio as well as to hyperosmotic cell shrinkage. In contrast, protection of VSMC from apoptosis by ouabain was abolished under equimolar substitution of Na + o with K + o , showing that the anti apoptotic action of Na + ,K + pump inhibition was caused by inversion of the intracellular Na + /K + ratio. Unlike VSMC, the same level of increment of the [Na + ] i /[K + ] i ratio caused by 2 hours preincubation of Jurkat cells with ouabain did not affect chromatin cleavage and caspase-3 activity triggered by treatment with Fas ligand, staurosporine or hyperosmotic shrinkage. Thus, our results show for the first time that similarly to cell proliferation, maintenance of a physiologically low intracellular Na + /K + ratio is required for progression of VSMC apoptosis.