Comprehensive Report on the Investigational Dual ATM/DNA-PK Inhibitor XRD-0394

1. Introduction to XRD-0394

XRD-0394 is a novel, orally bioavailable, small-molecule investigational drug candidate currently under development for the treatment of various cancers.[1] It represents a first-in-class therapeutic approach targeting the DNA Damage Response (DDR) pathway through the dual inhibition of two critical serine/threonine protein kinases: Ataxia Telangiectasia Mutated kinase (ATM) and DNA-dependent Protein Kinase catalytic subunit (DNA-PKcs).[1] This dual inhibitory action confers potential radiosensitizing and antineoplastic activities.[1]

The compound is being developed by XRad Therapeutics, Inc., a clinical-stage biopharmaceutical company specializing in the discovery and development of dual kinase inhibitors targeting DNA damage repair pathways for cancer therapy.[3] The initial clinical development strategy for XRD-0394 focuses on its potential to enhance the efficacy of radiation therapy (RT) when used in combination.[3] Concurrently, XRad Therapeutics is exploring the therapeutic potential of XRD-0394 in combination with other modalities, including targeted radionuclides, immune checkpoint inhibitors, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, and antibody-drug conjugates (ADCs).[3]

Chemically, XRD-0394 is identified by the CAS Number 2595308-10-2.[2] Its molecular formula is C26​H30​FN5​O4​S, corresponding to a molecular weight of 527.615 g/mol.[2] The IUPAC name is N-(5-(7'-fluoro-3'-methyl-2'-oxo-2',3'-dihydrospiro[cyclobutane-1,1'-pyrrolo[2,3-c]quinolin]-8'-yl)-2-(2-(isopropylamino)ethoxy)pyridin-3-yl)methanesulfonamide.[6] Synonyms include ataxia telangiectasia mutated kinase/DNA-dependent protein Kinase inhibitor XRD-0394, XRD 0394, and XRD0394.[1]

Table 1: Summary of XRD-0394 Key Information