AKT activation because of PTEN loss upregulates xCT via GSK3β/NRF2, leading to inhibition of ferroptosis in PTEN-mutant tumor cells.

Autor: Cahuzac KM; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Lubin A; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Bosch K; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Stokes N; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Shoenfeld SM; BluPrint Oncology, New Haven, CT, USA., Zhou R; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Lemon H; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Asara J; Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA, USA., Parsons RE; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: ramon.parsons@mssm.edu.

Publikováno v: Cell reports [Cell Rep] 2023 May 30; Vol. 42 (5), pp. 112536. Date of Electronic Publication: 2023 May 20.

Discovery of Potent, Selective, and In Vivo Efficacious AKT Kinase Protein Degraders via Structure-Activity Relationship Studies.

Autor: Yu X; Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Xu J; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Shen Y; Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Cahuzac KM; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Park KS; Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Dale B; Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Liu J; Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Parsons RE; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States., Jin J; Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2022 Feb 24; Vol. 65 (4), pp. 3644-3666. Date of Electronic Publication: 2022 Feb 04.

AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway-Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B.

Autor: Xu J; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Yu X; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York., Martin TC; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Bansal A; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Cheung K; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Lubin A; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Stratikopoulos E; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Cahuzac KM; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Wang L; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Xie L; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Zhou R; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Shen Y; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York., Wu X; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Yao S; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Qiao R; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Poulikakos PI; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Chen X; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Liu J; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York., Jin J; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York., Parsons R; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Publikováno v: Cancer discovery [Cancer Discov] 2021 Dec 01; Vol. 11 (12), pp. 3064-3089.