title: In silico identification and biological evaluation of novel selective serum/glucocorticoid-inducible kinase 1 inhibitors based on the pyrazolo-pyrimidine scaffold.
abstract: The serum/glucocorticoid-inducible kinase 1 (Sgk1) has demonstrated antiapoptotic function and the capability to regulate cell survival, proliferation, and differentiation. A pivotal role of Sgk1 in carcinogenesis and in resistance to anticancer therapy has been suggested. With the aim of identifying new Sgk1 modulators, 322 pyrazolo-pyrimidine derivatives have been virtually screened with respect to a crystallographic model of Sgk1. The top five ranked compounds have been evaluated demonstrating Sgk1 inhibition in vitro and selectivity compared to RAC-alpha serine/threonine-protein kinase (Akt1).
authors.affiliation: Departments of "Scienze della Salute" and ‡"Medicina Sperimentale e Clinica", University "Magna Græcia" of Catanzaro , Viale Europa Loc. Germaneto, 88100 Catanzaro, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Rosario
authors.initials: R
authors.lastname: Amato
authors.forename: Anna
authors.initials: A
authors.lastname: Artese
authors.forename: Lucia
authors.initials: L
authors.lastname: D'antona
authors.forename: Giosuè
authors.initials: G
authors.lastname: Costa
authors.forename: Cristina
authors.initials: C
authors.lastname: Talarico
authors.forename: Francesco
authors.initials: F
authors.lastname: Gigliotti
authors.forename: Cataldo
authors.initials: C
authors.lastname: Bianco
authors.forename: Francesco
authors.initials: F
authors.lastname: Trapasso
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Francesca
authors.initials: F
authors.lastname: Musumeci
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Botta
authors.forename: Nicola
authors.initials: N
authors.lastname: Perrotti
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
mesh_terms: D045744:Cell Line, Tumor; D003198:Computer Simulation; D055808:Drug Discovery; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C031280:pyrazole; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase; C030986:pyrimidine