Boffey, Helen K.; Rooney, Timothy P. C.; Willems, Henriette M. G.; Edwards, Simon; Green, Christopher; Howard, Tina; Ogg, Derek; Romero, Tamara; Scott, Duncan E.; Winpenny, David; Duce, James; Skidmore, John; Clarke, Jonathan H.; Andrews, Stephen P. published the artcile< Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode>, Computed Properties of 112-63-0, the main research area is PI5P4K gamma inhibitor allosteric binding mode crystal structure.
Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunol. disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochem. properties of the selective PI5P4Kγ inhibitor, NIH-12848 (1). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kβ. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chem. series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.
Journal of Medicinal Chemistry published new progress about Allosteric modulators. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Computed Properties of 112-63-0.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics