136616-35-8Relevant articles and documents
Discovery of novel anti-breast cancer agents derived from deguelin as inhibitors of heat shock protein 90 (HSP90)
Ann, Jihyae,Byun, Woong Sub,Kim, Ji Young,Kim, Yoon-Jae,Lee, Jeewoo,Lee, Sangkook,Nam, Gibeom,Nguyen, Cong-Truong,Park, Hyun-Ju,Park, Soeun,Sahu, Raghaba,Seo, Jae Hong
, (2020/07/15)
A series of O-substituted analogues of the B,C-ring truncated scaffold of deguelin were designed as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antiproliferative agents against HER2-positive breast cancer. Among the synthesized compounds, compound 80 exhibited significant inhibition in both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells, whereas compound 80 did not show any cytotoxicity in normal cells. Compound 80 markedly downregulated the expression of the major client proteins of HSP90 in both cell types, indicating that the cytotoxicity of 80 in breast cancer cells is attributed to the destabilization and inactivation of HSP90 client proteins and that HSP90 inhibition represents a promising strategy to overcome trastuzumab resistance. A molecular docking study of 80 with the homology model of a HSP90 homodimer showed that 80 fit nicely in the C-terminal domain with a higher electrostatic complementary score than that of ATP.
SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): Discovery of antagonist SB-568849
Witty, David R.,Bateson, John H.,Hervieu, Guillaume J.,Jeffrey, Phillip,Johnson, Christopher N.,Muir, Alison I.,O'Hanlon, Peter J.,Stemp, Geoffrey,Stevens, Alex J.,Thewlis, Kevin M.,Wilson, Shelagh,Winborn, Kim Y.
, p. 4865 - 4871 (2007/10/03)
We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were
