4693-01-0Relevant articles and documents
Design, synthesis and biological evaluation of E-ring modified evodiamine derivatives as novel antitumor agents
Fang, Kun,Dong, Guo-Qiang,Gong, Hai,Liu, Na,Li, Zhen-Gang,Zhu, Shi-Ping,Miao, Zhen-Yuan,Yao, Jian-Zhong,Zhang, Wan-Nian,Sheng, Chun-Quan
, p. 978 - 982 (2014)
A series of novel E-ring modified evodiamine derivatives were designed and synthesized as antitumor agents. Their capacity to interfere with the catalytic activity of topoisomerase I and II was evaluated by the relaxation assay. In vitro antitumor activity results revealed that compound 12 showed good antitumor activity with a broad spectrum. Its binding modes with topoisomerase I and II were clarified by molecular docking.
Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket
Bellenie, Benjamin R.,Bright, Michael D.,Burke, Rosemary,Carter, Michael,Cheung, Kwai-Ming J.,Collie, Gavin W.,Davis, Owen A.,Gatti Iou, Mahad,Gunnell, Emma,Hayes, Angela,Henley, Alan T.,Hoelder, Swen,Huckvale, Rosemary,Johnson, Louise D.,Le Bihan, Yann-Va?,Lloyd, Matthew G.,Mcandrew, P. Craig,Meniconi, Mirco,Pierrat, Olivier A.,Raynaud, Florence I.,Rodrigues, Matthew J.,Rossanese, Olivia W.,Talbot, Rachel,Van Montfort, Rob L. M.
, p. 17079 - 17097 (2021/12/13)
We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. Identifying potent inhibitors required not only forming new interactions in the subpocket but also perturbing the water network in a productive, potency-increasing fashion while controlling the physicochemical properties. We achieved this goal in a sequential manner by systematically probing the pocket and the water network, ultimately achieving a 100-fold improvement of activity. The most potent compounds displaced three of the five initial water molecules and formed hydrogen bonds with the remaining two. Compound 25 showed a promising profile for a lead compound with submicromolar inhibition of BCL6 in cells and satisfactory pharmacokinetic (PK) properties. Our work highlights the importance of finding productive ways to perturb existing water networks when growing into solvent-filled protein pockets.
Biotin-conjugated N-methylisatoic anhydride: A chemical tool for nucleic acid separation by selective 2′-hydroxyl acylation of RNA
Ursuegui,Chivot,Moutin,Burr,Fossey,Cailly,Laayoun,Fabis,Laurent
supporting information, p. 5748 - 5751 (2014/05/20)
An isatoic anhydride derivative conjugated to a biotin and a disulfide linker was specifically designed for the separation of nucleic acids. Starting from a DNA-RNA mixture, a selective 2′-hydroxyl acylation of RNAs followed by capture with streptavidin-coated magnetic beads and cleavage of the disulfide led to elution of RNAs. the Partner Organisations 2014.