Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring

0442570 - ÚMG 2015 RIV US eng J - Článek v odborném periodiku
Andrs, M. - Kobarecny, J. - Jun, D. - Hodný, Zdeněk - Bártek, Jiří - Kuca, K.
Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring.
Journal of Medicinal Chemistry. Roč. 58, č. 1 (2015), s. 41-71. ISSN 0022-2623. E-ISSN 1520-4804
Grant CEP: GA MŠMT(CZ) CZ.1.07/2.3.00/30.0044
Grant ostatní: University Hospital Hradec Kralove(CZ) 00179906; Faculty of Military Health Sciences, University of Defence(CZ) SV/FVZ201402
Institucionální podpora: RVO:68378050
Klíčová slova: DEPENDENT PROTEIN-KINASE * STRAND BREAK REPAIR * SELECTIVE PI3K-BETA INHIBITORS * TELANGIECTASIA MUTATED KINASE
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 5.589, rok: 2015

Phosphatidylinositol 3-kinases (PI3Ks) and phosphatidylinositol 3-kinase-related protein kinases (PIKKs) are two related families of kinases that play key roles in regulation of cell proliferation, metabolism, migration, survival, and responses to diverse stresses including DNA damage. To design novel efficient strategies for treatment of cancer and other diseases, these kinases have been extensively studied. Despite their different nature, these two kinase families have related origin and share very similar kinase domains. Therefore, chemical inhibitors of these kinases usually carry analogous structural motifs. The most common feature of these inhibitors is a critical hydrogen bond to morpholine oxygen, initially present in the early nonspecific PI3K and PIKK inhibitor 3 (LY294002), which served as a valuable chemical tool for development of many additional PI3K and PIKK inhibitors. While several PI3K pathway inhibitors have recently shown promising clinical responses, inhibitors of the DNA damage-related PIKKs remain thus far largely in preclinical development.
Trvalý link: http://hdl.handle.net/11104/0245400