On April 8, 2015, Lee, Changwook; Park, Hye-Kyung; Jeong, Hanbin; Lim, Jaehwa; Lee, An-Jung; Cheon, Keun Young; Kim, Chul-Su; Thomas, Ajesh P.; Bae, Boram; Kim, Nam Doo; Kim, Seong Heon; Suh, Pann-Ghill; Ryu, Ja-Hyoung; Kang, Byoung Heon published an article.Formula: C24H27Br2P The title of the article was Development of a Mitochondria-Targeted Hsp90 Inhibitor Based on the Crystal Structures of Human TRAP1. And the article contained the following:
The mitochondrial pool of Hsp90 and its mitochondrial paralog, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. Here, the authors report that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibitors cannot effectively inactivate TRAP1 because of their insufficient accumulation in the mitochondria. To develop mitochondrial TRAP1 inhibitors, the authors determined the crystal structures of human TRAP1 complexed with Hsp90 inhibitors. The iso-Pr amine of the Hsp90 inhibitor PU-H71 was replaced with the mitochondria-targeting moiety triphenylphosphonium to produce SMTIN-P01. SMTIN-P01 showed a different mode of action from the nontargeted PU-H71, as well as much improved cytotoxicity to cancer cells. In addition, the authors determined the structure of a TRAP1-adenylyl-imidodiphosphate (AMP-PNP) complex. On the basis of comparative anal. of TRAP1 structures, the authors propose a mol. mechanism of ATP hydrolysis that is crucial for chaperone function. The experimental process involved the reaction of (6-Bromohexyl)triphenylphosphonium bromide(cas: 83152-22-1).Formula: C24H27Br2P
The Article related to mitochondria hsp inhibitor crystal structure trap, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Formula: C24H27Br2P
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