Senior Recital, Ryan Moses, piano

The presentation of this senior recital will fulfill in part the requirements for the Bachelor of Music degree in Jazz Studies. Ryan Moses studies jazz piano with Wells Hanley

Senior Recital, Logan T. Beaver, saxophone

The presentation of this senior recital will fulfill in part the requirements for the Bachelor of Music degree in Jazz Studies. Logan T. Beaver studies saxophone with J.C. Kuhl and Skip Gailes

Structure-based Design of Pyridone–Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition

Dysregulated translation of mRNA plays a major role in tumorigenesis. Mitogen-activated protein kinase interacting kinases (MNK)­1/2 are key regulators of mRNA translation integrating signals from oncogenic and immune signaling pathways through phosphorylation of eIF4E and other mRNA binding proteins. Modulation of these key effector proteins regulates mRNA, which controls tumor/stromal cell signaling. Compound <b>23</b> (eFT508), an exquisitely selective, potent dual MNK1/2 inhibitor, was designed to assess the potential for control of oncogene signaling at the level of mRNA translation. The crystal structure-guided design leverages stereoelectronic interactions unique to MNK culminating in a novel pyridone–aminal structure described for the first time in the kinase literature. Compound <b>23</b> has potent <i>in vivo</i> antitumor activity in models of diffuse large cell B-cell lymphoma and solid tumors, suggesting that controlling dysregulated translation has real therapeutic potential. Compound <b>23</b> is currently being evaluated in Phase 2 clinical trials in solid tumors and lymphoma. Compound <b>23</b> is the first highly selective dual MNK inhibitor targeting dysregulated translation being assessed clinically

Structure-based Design of Pyridone–Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition

Dysregulated translation of mRNA plays a major role in tumorigenesis. Mitogen-activated protein kinase interacting kinases (MNK)­1/2 are key regulators of mRNA translation integrating signals from oncogenic and immune signaling pathways through phosphorylation of eIF4E and other mRNA binding proteins. Modulation of these key effector proteins regulates mRNA, which controls tumor/stromal cell signaling. Compound <b>23</b> (eFT508), an exquisitely selective, potent dual MNK1/2 inhibitor, was designed to assess the potential for control of oncogene signaling at the level of mRNA translation. The crystal structure-guided design leverages stereoelectronic interactions unique to MNK culminating in a novel pyridone–aminal structure described for the first time in the kinase literature. Compound <b>23</b> has potent <i>in vivo</i> antitumor activity in models of diffuse large cell B-cell lymphoma and solid tumors, suggesting that controlling dysregulated translation has real therapeutic potential. Compound <b>23</b> is currently being evaluated in Phase 2 clinical trials in solid tumors and lymphoma. Compound <b>23</b> is the first highly selective dual MNK inhibitor targeting dysregulated translation being assessed clinically