A Novel Dual ATM/DNA-PK Inhibitor, XRD-0394, Potently Radiosensitizes and Potentiates PARP and Topoisomerase I Inhibitors

Dual ATM/DNA-PK inhibitor XRD-0394 featured in publication highlighting its radiosensitizing potential in preclinical cancer research.

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Authors: Tona M Gilmer, Chun-Hsiang Lai, Kexiao Guo, Katherine Deland, Kathleen A. Ashcraft, Amy E Stewart, Yaode Wang, Jianmin Fu, Kris C. Wood, David G. Kirsch, Michael B. Kastan

This study highlights the discovery and preliminary evaluation of XRD-0394, an orally administered compound that not only radiosensitizes cancer cells but also increases the activity of topoisomerase I inhibitors under laboratory conditions. Furthermore, XRD-0394 demonstrates single-agent efficacy in BRCA1/2-deficient cells and exhibits synergistic effects when combined with PARP inhibitors.

A Phase Ia clinical study (NCT05002140) evaluating kinase inhibitor XRD-0394 in combination with radiotherapy has been successfully completed, showcasing its potential in advanced cancer treatments.

Pharmaron played a pivotal role in this study by providing integrated drug discovery services, including:

  • Design of novel target molecules using computer-aided drug discovery (CADD)
  • Synthesis of newly designed compounds
  • Evaluation of compounds’ in vitro activities
  • DMPK studies on promising compounds

Mol Cancer Ther. 2024 Jun 4;23(6):751-765.

DOI: 10.1158/1535-7163.MCT-23-0890

Access the publication at:https://pubmed.ncbi.nlm.nih.gov/38588408/