ArticleMolecular cancer therapeutics2018
Orally Bioavailable and Blood-Brain Barrier-Penetrating ATM Inhibitor (AZ32) Radiosensitizes Intracranial Gliomas in Mice.
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Article in Molecular cancer therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- The Development of ATM Inhibitors in Cancer Therapy.Targeted oncology · 2025Review
- ATM Kinase Small Molecule Inhibitors Prevent Radiation-Induced Apoptosis of Mouse Neurons In Vivo.Kinases and phosphatases · 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
- Preclinical Systemic Pharmacokinetics, Dose Proportionality, and Central Nervous System Distribution of the ATM Inhibitor WSD0628, a Novel Radiosensitizer for the Treatment of Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2024Article
- Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization.Science translational medicine · 2024Article
- Identification of DNA methylation-regulated WEE1 with potential implications in prognosis and immunotherapy for low-grade glioma.Cancer biomarkers : section A of Disease markers · 2024Article
- Discovery of [1,2,3]Triazolo[4,5-ACS medicinal chemistry letters · 2023Article
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- RPRM negatively regulates ATM levels through its nuclear translocation on irradiation mediated by CDK4/6 and IPO11.iScience · 2022Article
- Article
- Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2022Article
- Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma.Molecular therapy oncolytics · 2022Article
- Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma.Cancers · 2022Review
- Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.Nature reviews. Clinical oncology · 2022Review
- Targeting Cell Cycle Checkpoint Kinases to Overcome Intrinsic Radioresistance in Brain Tumor Cells.Cancers · 2022Review
- Review
- Genotoxic therapy and resistance mechanism in gliomas.Pharmacology & therapeutics · 2021Review
- DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets.Cellular oncology (Dordrecht, Netherlands) · 2021Review
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Authors and funding
36 authors at 2 institutions in 2 countries.
Jeremy Karlin *Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Jasmine Allen *Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Syed F AhmadDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Gareth HughesAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Victoria SheridanAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Rajesh OdedraAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Paul FarringtonAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Elaine B CadoganAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Lucy C RichesAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Antonio Garcia-TrinidadAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Andrew G ThomasonAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Bhavika PatelAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Jennifer VincentAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Alan LauAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Kurt G PikeAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Thomas A HuntAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Amrita SuleDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Nicholas C K ValerieDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Laura Biddlestone-ThorpeDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Jenna KahnDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Jason M BecktaDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Nitai MukhopadhyayDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
Bernard BarlaamAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Sebastien L DegorceAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Jason KettleAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Nicola ColcloughAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Joanne WilsonAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Aaron SmithAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Ian P BarrettAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Li ZhengAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Tianwei ZhangAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Yingchun WangAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Kan ChenAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Martin PassAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Stephen T DurantAstraZeneca - Bioscience, DMPK, Chemistry, Discovery Sciences and Projects-Oncology, IMED Biotech Unit, Alderley Park, Cambridge, United Kingdom; and DizalPharma, Shanghai, China.
Kristoffer ValerieDepartment of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia. kristoffer.valerie@vcuhealth.org.
AstraZeneca (United Kingdom) · GBVirginia Commonwealth University · US
Funding
Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0MATM as target for malignant glioma radiosensitization.R01NS064593 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI VALERIE, KRISTOFFER CARL · 2009 to 2013
$1.7MNovel, orally available ATM inhibitor for glioma conformal radiosensitizationR21CA194789 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI VALERIE, KRISTOFFER CARL · 2016 to 2017
$365kGAMMACELL 40 137 CS IRRADIATORS10RR022443 · NCRR · VIRGINIA COMMONWEALTH UNIVERSITY · PI VALERIE, KRISTOFFER CARL · 2006 to 2006
$361kTargeting invasion and DNA DSB repair in glioma with a multi-pronged approach.R21CA156995 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI VALERIE, KRISTOFFER CARL · 2011 to 2012
$358kNCI NIH HHS P30 CA016059NCI NIH HHS R21 CA156995NCI NIH HHS R21 CA194789NCRR NIH HHS S10 RR022443NINDS NIH HHS R01 NS064593
Abstract
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited central nervous system (CNS) bioavailability; thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested
Indexed as
Administration, OralAnimalsAtaxia Telangiectasia Mutated ProteinsBlood-Brain BarrierCell Line, TumorGliomaHumansMiceMice, NudeProtein Kinase InhibitorsRadiation-Sensitizing AgentsAtaxia Telangiectasia Mutated ProteinsAtm protein, mouseProtein Kinase InhibitorsRadiation-Sensitizing Agents
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.