Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
Our study did not show significant benefits for the use of US to guide arterial femoral access compared to the anatomical landmark approach, but pooled analysis of five randomized trials showed decreased rates of bleeding events and venipunctures, and improved first-pass success. The clinical impact of these findings is uncertain, and do not warrant a systematic use of US-guidance in this clinical setting.
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