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    DRUG:

    ceralasertib (AZD6738)

    i
    Other names: AZD6738, AZD 6738, AZD-6738
    Company:
    AstraZeneca
    Drug class:
    ATR inhibitor
    Related drugs:
    4d
    ATR inhibitors: from targeting the DNA damage response to exploiting synthetic lethality-A paradigm shift in Cancer therapy. (PubMed, Bioorg Chem)
    We provide a detailed analysis of the structure-activity relationships (SAR) of leading clinical candidates, including berzosertib, ceralasertib, and elimusertib, focusing on strategic chemical modifications such as scaffold hopping and sulfoximine substitution to optimize selectivity and druggability. Critical challenges, specifically dose-limiting hematological toxicities and acquired resistance, are analyzed alongside the search for robust predictive biomarkers. By synthesizing current pharmacological and clinical data, this work outlines the trajectory for next-generation ATR-targeted precision medicine.
    Review • Journal
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    ATR (Ataxia telangiectasia and Rad3-related protein)
    |
    berzosertib (M6620) • ceralasertib (AZD6738) • elimusertib (BAY 1895344)
    5d
    Loss of BOK increases vulnerability of p53 deficient non-small cell lung cancer cells to ATR inhibition through its role in uridine metabolism. (PubMed, Cell Death Differ)
    We exploited this vulnerability by inhibiting the ATR-mediated DNA damage response pathway with the selective ATR inhibitor ceralasertib (AZD6738)...Given the frequent inactivation of p53 in lung cancer, our study offers a rationale for clinical exploration of ATR inhibitors, in combination with standard chemotherapy, in the context of reduced BOK function. Future investigations into the broader role of BOK in genomic stability and nucleotide metabolism may uncover additional therapeutic strategies for cancers with repressed BOK.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2)
    |
    ceralasertib (AZD6738)
    7d
    Recent advances in small molecule ATR kinase inhibitors as anticancer agents. (PubMed, Future Med Chem)
    Over the last decade, intensive medicinal chemistry efforts have generated a broad pipeline of ATR inhibitors, including ceralasertib, elimusertib, camonsertib, berzosertib, ART0380, and gartisertib, many of which are in Phase I/II clinical trials. Incorporating these strategies into adaptive platform trials with pharmacodynamic markers and patient-centered outcomes will speed up translation. Overall, ATR inhibitors highlight progress in DNA damage response therapies, from understanding mechanisms to biomarker-driven clinical use, with the potential to revolutionize treatment across various cancers.
    Review • Journal • PARP Biomarker • IO biomarker
    |
    RAD51 (RAD51 Homolog A)
    |
    berzosertib (M6620) • ceralasertib (AZD6738) • elimusertib (BAY 1895344) • alnodesertib (ART0380) • camonsertib (RP-3500) • gartisertib (M4344)
    7d
    An Inducible BRCA1 Expression System with In Vivo Applicability Uncovers Activity of the Combination of ATR and PARP Inhibitors to Overcome Therapy Resistance. (PubMed, Cancers (Basel))
    Our findings identify a dose-dependent, hypomorphic HRR restoration by ∆exon11 BRCA1, help explain the variable resistance observed in BRCA1-mutant pre-clinical models expressing this hypomorph, and propose ATR inhibition in combination with PARPi as a clinical strategy to counteract therapeutic resistance mediated by ∆exon11 BRCA1 hypomorphs.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A)
    |
    Lynparza (olaparib) • carboplatin • ceralasertib (AZD6738)
    8d
    Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=630, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Checkpoint inhibition
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    12d
    A Study to Evaluate the Effect of Ceralasertib on Drug X, Drug Y and Drug Z (clinicaltrials.gov)
    P1, N=1, Terminated, AstraZeneca | N=20 --> 1 | Recruiting --> Terminated; The study terminated because the clinical development programme for Ceralasertib has been discontinued.
    Enrollment change • Trial termination
    |
    ceralasertib (AZD6738)
    18d
    Novel therapeutic potential of the PARP inhibitor talazoparib in synovial sarcoma and its combined effect with ATR inhibitor. (PubMed, Discov Oncol)
    Talazoparib combined with ATR inhibitor possesses potential application as a therapeutic option for SS.
    Journal • PARP Biomarker
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    CHEK1 (Checkpoint kinase 1) • ANXA5 (Annexin A5)
    |
    Talzenna (talazoparib) • ceralasertib (AZD6738)
    20d
    EFFORT: Adavosertib With or Without Olaparib in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov)
    P2, N=96, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD • BRCA mutation
    |
    Lynparza (olaparib) • adavosertib (AZD1775) • ceralasertib (AZD6738)
    28d
    Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C. (PubMed, Br J Cancer)
    PMDOs can be completely eradicated if MMC treatment is followed by inhibition of ATR or other DDR kinases. DDR inhibitors may therefore have value in the adjuvant treatment of peritoneal metastases following CRS-HIPEC.
    Journal
    |
    CHEK1 (Checkpoint kinase 1)
    |
    oxaliplatin • adavosertib (AZD1775) • irinotecan • berzosertib (M6620) • ceralasertib (AZD6738) • elimusertib (BAY 1895344) • mitomycin • rabusertib (LY 2603618)
    2ms
    AUSTRAL: Phase II Study of Radiotherapy Followed by Durvalumab and Ceralasertib in Stage III NSCLC Patients With Thoracic Relapses +/- Oligometastases After PACIFIC Regimen (clinicaltrials.gov)
    P2, N=21, Recruiting, Mario Negri Institute for Pharmacological Research | Not yet recruiting --> Recruiting | Trial completion date: Jan 2028 --> Jan 2029 | Trial primary completion date: Jan 2027 --> Jun 2028
    Enrollment open • Trial completion date • Trial primary completion date
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    2ms
    A Study to Evaluate the Safety and Pharmacokinetics of Ceralasertib in Combination With Durvalumab in Chinese Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, AstraZeneca | Trial completion date: Oct 2025 --> Mar 2026
    Trial completion date
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)