1/21/2010 (Thu) 第一次討論會議
Speaker 1-北醫劉景平: Structures of 292, J-30, SAHA etc. One OCH3 group in 292 is enough, two OCH3 increases IC50 from 50 nM to 1400 nM; replace with OH increases IC50 from 50 nM to 500 nM. SAHA is a planer structure, quite stable. SAHA is a pan-HDACi, with uM range. B291 is also a pan-HDACi, with 100 nM range. Wishing 292 is more specific.
Speaker 2-程韻靜: Effects of 292 (1/3) inhibits tubulin polymerization in KB cell; (2/3) inhibits tube formation in SH-SY5Y; (3/3) Animal models (CAM, xenograft in H460 58.7% inhibition, orthotopic PANC-1 with Luc expression); Calcium influx was increased in Taxol or J-30 (not as good as Taxol) treated neuronal cells, but neither SAHA nor 292 had effects in calcium influx; While most cells exhibit 50~100 nM IC50, HUVEC is 42 uM and WI-38 is 12 uM (so interesting!!!)
Speaker 3-夏興國: (1) B292 and EMT seemed not have correlation in breast and lung cancer cells (2) B292 and Adhesion: CL1-0 扁平+292 (uM) =扁平. CL1-5 細長+292 (nM)=morphological changes and tubulin disperse…. (但butyrate, TSA, SAHA都能造成相同現象(FAK and paxillin increases) 耶…
Speaker 4-吳仲峻: TWO1 (72 nM), NA (35 nM with EAD 5~10%), HONE-1 (66 nM), HA (42 nM).
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11/1/09 SFL wrote:
與PrCA/AR有關:Taken together, our studies suggest that HDAC6 regulates AR hypersensitivity and nuclear localization, mainly via modulating HSP90 acetylation.
與Tau有關:To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation.
有空要瞭解一下HSP90,就這麼查吧. “hsp90 review AND cell cycle [jour]”
SAHA 相關 Chiang’s recent paper [Here].