Can I read Discovery of a Potent Chloroacetamide GPX4 Inhibitor with Bioavailability to Enable Target Engagement in Mice, a Potential Tool Compound for Inducing Ferroptosis In Vivo on EtoBox?

Discovery of a Potent Chloroacetamide GPX4 Inhibitor with Bioavailability to Enable Target Engagement in Mice, a Potential Tool Compound for Inducing Ferroptosis In Vivo by John T. Randolph; Matthew J. O’Connor; Fei Han; Charles W. Hutchins; Y. Amy Siu; Min Cho; Yunan Zheng; Jonathan A. Hickson; Jana L. Markley; Vlasios Manaves; Mikkel Algire; Kenton A. Baker; Alex M. Chapman; Sujatha M. Gopalakrishnan; Sanjay C. Panchal; Kelly Foster-Duke; DeAnne F. Stolarik; Anita Kempf-Grote; Darby Dammeier; Stacey Fossey; Qi Sun; Chaohong Sun; Yu Shen; Michael J. Dart; Warren M. Kati; Albert Lai; Ari J. Firestone; Michael E. Kort is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Discovery of a Potent Chloroacetamide GPX4 Inhibitor with Bioavailability to Enable Target Engagement in Mice, a Potential Tool Compound for Inducing Ferroptosis In Vivo about?

Compounds that inhibit glutathione peroxidase 4 (GPX4) hold promise as cancer therapeutics in their ability to induce a form of nonapoptotic cell death called ferroptosis. Our research identified 24, a structural analog of the potent GPX4 inhibitor RSL3, that has much better plasma stability (t 1/2 > 5 h in mouse plasma). The bioavailability of 24 provided efficacious plasma drug concentrations with IP dosing, thus enabling in vivo studies to assess tolerability and efficacy. An efficacy study in mouse using a GPX4-sensitive tumor model found that doses of 24 up to 50 mg/kg were tolerated for 20 days but had no effect on tumor growth, although partial target engagement was observed in tumor homogenate.

Who reads Discovery of a Potent Chloroacetamide GPX4 Inhibitor with Bioavailability to Enable Target Engagement in Mice, a Potential Tool Compound for Inducing Ferroptosis In Vivo?

Author

John T. Randolph; Matthew J. O’Connor; Fei Han; Charles W. Hutchins; Y. Amy Siu; Min Cho; Yunan Zheng; Jonathan A. Hickson; Jana L. Markley; Vlasios Manaves; Mikkel Algire; Kenton A. Baker; Alex M. Chapman; Sujatha M. Gopalakrishnan; Sanjay C. Panchal; Kelly Foster-Duke; DeAnne F. Stolarik; Anita Kempf-Grote; Darby Dammeier; Stacey Fossey; Qi Sun; Chaohong Sun; Yu Shen; Michael J. Dart; Warren M. Kati; Albert Lai; Ari J. Firestone; Michael E. Kort

Publisher

American Chemical Society (ACS)

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)