951006-27-2Relevant academic research and scientific papers
Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
Sellers, Robert P.,Alexander, Leslie D.,Johnson, Victoria A.,Lin, Chun-Chieh,Savage, Jeremiah,Corral, Ricardo,Moss, Jason,Slugocki, Tim S.,Singh, Erinprit K.,Davis, Melinda R.,Ravula, Suchitra,Spicer, Jamie E.,Oelrich, Jenna L.,Thornquist, Andrea,Pan, Chung-Mao,McAlpine, Shelli R.
experimental part, p. 6822 - 6856 (2010/10/18)
Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.
A comprehensive study of Sansalvamide A derivatives: The structure-activity relationships of 78 derivatives in two pancreatic cancer cell lines
Pan, Po-Shen,Vasko, Robert C.,Lapera, Stephanie A.,Johnson, Victoria A.,Sellers, Robert P.,Lin, Chun-Chieh,Pan, Chung-Mao,Davis, Melinda R.,Ardi, Veronica C.,McAlpine, Shelli R.
experimental part, p. 5806 - 5825 (2009/12/24)
We report an extensive structure-activity relationship (SAR) of 78 compounds active against two pancreatic cancer cell lines. Our comprehensive evaluation of these compounds utilizes SAR that allow us to evaluate which features of potent compounds play a
