ArticleCancer chemotherapy and pharmacology2022
Dose-dependent bioavailability, absorption-rate limited elimination, and tissue distribution of the ATR inhibitor BAY-1895344 (elimusertib) in mice.
Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 7 citations in OpenAlex.
- Black Rice Anthocyanin-Hyaluronic Acid Complex Alleviates Hyperuricemia-Associated Renal Injury Through Synergistic Inhibition of the TLR4/NF-κB Pathway and Modulation of Uric Acid Transport.Molecular nutrition & food research · 2026Article
- Transient ATR inhibition following ionizing radiation enhances immune-mediated antitumor response and survival.bioRxiv : the preprint server for biology · 2026Article
- Article
- Comparative in vivo toxicology of ATR inhibitors ceralasertib, elimusertib, and berzosertib alone and in combination with ionizing radiation.Toxicology and applied pharmacology · 2025Article
- Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).Cancer chemotherapy and pharmacology · 2025Article
- Factors Influencing the Central Nervous System (CNS) Distribution of the Ataxia Telangiectasia Mutated and Rad3-Related Inhibitor Elimusertib (BAY1895344): Implications for the Treatment of CNS Tumors.The Journal of pharmacology and experimental therapeutics · 2024Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- Non-linear IV pharmacokinetics of the ATR inhibitor berzosertib (M6620) in mice.Cancer chemotherapy and pharmacology · 2024Article
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAtaxia Telangiectasia and Rad3-related (ATR) is a pivotal component of the DNA damage response and repair pathways that is activated in responses to cytotoxic cancer treatments. Several ATR inhibitors (ATRi) are in development that block the ATR mediated DNA repair and enhance the damage associated with cytotoxic therapy. BAY-1895344 (elimusertib) is an orally available ATRi with preclinical efficacy that is in clinical development. Little is known about the pharmacokinetics (PK) which is of interest, because tissue exposure and ATR inhibition may relate to toxicities or responses.
methodsTo evaluate BAY-1895344 PK, a sensitive LC-MS/MS method was utilized for quantitation in mouse plasma and tissues. PK studies in mice were first conducted to determine dose linearity. In vivo metabolites were identified and analyzed semi-quantitatively. A compartmental PK model was developed to describe PK behavior. An extensive PK study was then conducted in tumor-bearing mice to quantitate tissue distribution for relevant tissues.
resultsDose linearity was observed from 1 to 10 mg/kg PO, while at 40 mg/kg PO bioavailability increased approximately fourfold due to saturation of first-pass metabolism, as suggested by metabolite analyses and a developed compartmental model. Longer half-lives in PO treated mice compared to IV treated mice indicated absorption-rate limited elimination. Tissue distribution varied but showed extensive distribution to bone marrow, brain, and spinal cord.
conclusionsComplex PK behavior was limited to absorption processes which may not be recapitulated clinically. Tissue partition coefficients may be used to contrast ATR inhibitors with respect to their efficacy and toxicity.
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Registered trials
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