620596-79-4Relevant academic research and scientific papers
Drug Design and Synthesis of First in Class PDZ1 Targeting NHERF1 Inhibitors as Anticancer Agents
Coluccia, Antonio,La Regina, Giuseppe,Naccarato, Valentina,Nalli, Marianna,Orlando, Viviana,Biagioni, Stefano,De Angelis, Maria Laura,Baiocchi, Marta,Gautier, Candice,Gianni, Stefano,Di Pastena, Fiorella,Di Magno, Laura,Canettieri, Gianluca,Coluccia, Addolorata Maria Luce,Silvestri, Romano
supporting information, p. 499 - 503 (2019/04/25)
Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents.
Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a
Onda, Kenichi,Suzuki, Takayuki,Shiraki, Ryota,Yonetoku, Yasuhiro,Negoro, Kenji,Momose, Kazuhiro,Katayama, Naoko,Orita, Masaya,Yamaguchi, Tomohiko,Ohta, Mitsuaki,Tsukamoto, Shin-ichi
, p. 5452 - 5464 (2008/12/21)
A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC50 of 0.90 μM. The pyridine analogue of 2f showed inhibitory activity of glucagon-induced glucose output in cultured primary hepatocytes with an IC50 of 0.62 μM and oral hypoglycemic activity in diabetic db/db mice. Crystallographic determination of the complex of 2f with hLGPa showed binding of the inhibitor in a solvent cavity at the dimer interface, with the two hydroxyl groups making favorable electrostatic interactions with hLGPa.
