Hailey J. Knox

Abstract P4-12-19: Preclinical Characterization of a Novel PI3Kα H1047R Mutant-Selective Inhibitor

Aaron C. T. Smith, Ben Arwood-Levine, Abiezer Blandon, Alexandra Born et autres

Abstract PIK3CA encodes the p110α catalytic subunit of PI3-kinase alpha (PI3Kα) and is the most frequently mutated kinase in human cancer with common mutations occurring in the kinase domain (H1047R) and helical domain (E542K/E545K). The approved PI3Kα inhibitor, alpelisib, shows promise for …

Abstract 3004: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitor

Aaron C. T. Smith, Ben Arwood-Levine, Abiezer Blandon, Alexandra Born et autres

Abstract PIK3CA encodes the p110α catalytic subunit of PI3-kinase alpha (PI3Kα) and is the most frequently mutated kinase in human cancer with common mutations occurring in the kinase domain (H1047R) and helical domain (E542K/E545K). The approved PI3Kα inhibitor, alpelisib, shows promise for …

Exploring Biliverdin’s Molecular Interactions with Cu- and Fe-Based MOFs: A Unified In Vitro Study with Photoacoustic Analysis

Hamideh Rezvani Alanagh, Parinaz Fathi, Hailey J. Knox, Parikshit Moitra et autres

Metal–organic frameworks (MOFs) have shown promise in enhancing the stability of biomolecules. Herein, biliverdin (BVD), a photoacoustic (PA) and fluorescent agent, was immobilized within the pores of NH 2 -MIL-101 (Fe) (FeMOFs) and on the surface of CuBTC crystallites (CuMOFs). MOFs were …

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Inspiring a convergent engineering approach to measure and model the tissue microenvironment

Rishyashring R. Iyer, Catherine C. Applegate, Opeyemi H. Arogundade, Sushant Bangru et autres

Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics …

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Abstract PO3-26-01: Preclinical in vitro and in vivo characterization of a novel, wild-type-sparing, PI3Kα H1047R mutant-selective inhibitor

Aaron C. T. Smith, Ben Arwood-Levine, Alexandra Born, Richard K. Brizendine et autres

Abstract The PI3K pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. Specifically, the H1047R and helical domain mutations E542K/E545K of the p110α subunit of PI3K are known activating mutations that are targeted …

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Abstract 1440: Identification of a novel EGFR sparing brain penetrant ErbB2 inhibitor with activity against oncogenic ErbB2 mutations

Mark Joseph Chicarelli, Karyn Bouhana, Richard K. Brizendine, LouAnn Cable et autres

Abstract Oncogenic driver mutations in ErbB2 (e.g., S310F/Y, L755S, V777L, V842I) are present in a variety of tumor types including gastric, uterine, urothelial carcinoma, non-small cell lung, breast, and colorectal, some of which are also known to metastasize to the CNS. These …

Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane

Aaron L. Nichols, Zack Blumenfeld, Laura Luebbert, Hailey J. Knox et autres

Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed treatment for individuals experiencing major depressive disorder. The therapeutic mechanisms that take place before, during, or after SSRIs bind the serotonin transporter (SERT) are poorly understood, partially because no studies exist on the …

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Correction: Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands

Aaron L. Nichols, Zack Blumenfeld, Chengcheng Fan, Laura Luebbert et autres

Characterization of Binding Site Interactions and Selectivity Principles in the α3β4 Nicotinic Acetylcholine Receptor

Hailey J. Knox, Hugo Rego Campello, Henry A. Lester, Timothy C. Gallagher et autres

Nicotinic acetylcholine receptors (nAChRs) play an important role in neurotransmission and are also involved in addiction and several disease states. There is significant interest in therapeutic targeting of nAChRs; however, achieving selectivity for one subtype over others has been a longstanding challenge, …

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Selective Serotonin Reuptake Inhibitors Within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane

Aaron L. Nichols, Zack Blumenfeld, Laura Luebbert, Hailey J. Knox et autres

ABSTRACT Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed treatment for individuals experiencing major depressive disorder (MDD). The therapeutic mechanisms that take place before, during, or after SSRIs bind the serotonin transporter (SERT) are poorly understood, partially because no studies exist …

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Three Mutations Convert the Selectivity of a Protein Sensor from Nicotinic Agonists to S-Methadone for Use in Cells, Organelles, and Biofluids

Anand K. Muthusamy, Charlene H. Kim, Scott C. Virgil, Hailey J. Knox et autres

We report a reagentless, intensity-based S-methadone fluorescent sensor, iS-methadoneSnFR, consisting of a circularly permuted GFP inserted within the sequence of a mutated bacterial periplasmic binding protein (PBP). We evolved a previously reported nicotine-binding PBP to become a selective S-methadone-binding sensor, via three …

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Three Mutations Convert the Selectivity of a Protein Sensor from Nicotinic Agonists to S-methadone for Use in Cells, Organelles, and Biofluids

Anand K. Muthusamy, Charlene H. Kim, Scott C. Virgil, Hailey J. Knox et autres

ABSTRACT We report a reagentless, intensity-based S-methadone fluorescent sensor, iS-methadoneSnFR, consisting of a circularly permuted GFP inserted within the sequence of a mutated bacterial periplasmic binding protein (PBP). We evolved a previously reported nicotine-binding PBP to become a selective S-methadone-binding sensor, via …

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