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    DRUG:

    fexagratinib (ABSK091)

    i
    Other names: ABSK091, AZD4547, AZD 4547, ABSK-091
    Company:
    Abbisko, AstraZeneca
    Drug class:
    pan-FGFR inhib
    Related drugs:
    28d
    Establishment and characterization of preclinical models of human gynecologic tract carcinosarcomas demonstrates targetable FGFR1 alterations. (PubMed, Transl Oncol)
    These findings demonstrate the utility of patient-derived tumor models in the identification and the functional validation of potentially targetable molecular alterations in preclinical setting.
    Preclinical • Journal
    |
    TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1)
    |
    TP53 mutation
    |
    fexagratinib (ABSK091)
    29d
    Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities. (PubMed, Cell Death Discov)
    CAFs exhibited broad sensitivity to multikinase inhibitors, with dasatinib, midostaurin, and FGFR inhibitors (AZD4547, erdafitinib) emerging as top stromal-directed candidates. These findings underscore the plasticity of prostate CAFs and reveal actionable vulnerabilities, supporting the development of targeted stromal therapies to disrupt tumor-stroma interactions in PCa.
    Preclinical • Journal
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3) • CAV1 (Caveolin 1)
    |
    dasatinib • Balversa (erdafitinib) • midostaurin • fexagratinib (ABSK091)
    1m
    Development and Validation of a 7-eRNA Prognostic Signature for Lung Adenocarcinoma. (PubMed, Biology (Basel))
    Somatic mutation profiling highlighted TP53 and TTN as frequently mutated genes, while drug sensitivity prediction identified four potential therapeutic agents (including AZD4547 and Nutlin-3a) for high-risk individuals. Collectively, this study constructed a 7-eRNA prognostic model for LUAD, providing a powerful tool for clinical risk assessment and uncovering eRNA-mediated regulatory mechanisms.
    Journal
    |
    TP53 (Tumor protein P53) • TTN (Titin)
    |
    TP53 mutation
    |
    fexagratinib (ABSK091)
    1m
    Deciphering lactate/lactylation networks in AML: integrated scRNA-seq and transcriptomics reveal functions and prognostic model. (PubMed, BMC Cancer)
    Transcriptomic profiling indicated lactylation-associated immunosuppression (e.g., downregulated CXCL9/10-CXCR3 axis, enrichment of T cell exhaustion markers) and heightened in silico-predicted sensitivity to BCL-2/FGFR inhibitors (ABT-737/AZD4547) in high-risk patients. Collectively, integrated analyses uncovered lactate/lactylation-associated heterogeneity in AML. Our machine learning-based prognostic model predicts survival, therapeutic response, and drug sensitivity, suggesting a potential strategy for precision therapeutics in AML.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • ARPP19 (CAMP Regulated Phosphoprotein 19) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • IFI16 (Interferon Gamma Inducible Protein 16)
    |
    fexagratinib (ABSK091) • ABT-737
    2ms
    Dual-parameter tomographic imaging of attenuation and backscattering coefficients for quantitative evaluation of immune cell-mediated cytotoxicity in tumor spheroids. (PubMed, Theranostics)
    This approach enables high-resolution measurements of structural and optical property changes associated with apoptosis, allowing spatial and temporal mapping of treatment-induced cytotoxicity in HER2-positive breast tumor spheroids treated with AZD4547 and HER2-targeted chimeric antigen receptor (CAR) T cells... This dual-parameter OCT-based assay framework provides a sensitive, label-free method for distinguishing between immune- and drug-induced apoptosis in tumor spheroids. Its strong correlation with viability and capacity to resolve spatially resolved dynamics underscore its potential for robust, in situ assessment of immunotherapeutic efficacy.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    fexagratinib (ABSK091)
    2ms
    NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov)
    P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability) • CD4 (CD4 Molecule)
    |
    Opdivo (nivolumab) • Herceptin (trastuzumab) • Mekinist (trametinib) • Xalkori (crizotinib) • Tagrisso (osimertinib) • Gilotrif (afatinib) • Ibrance (palbociclib) • dasatinib • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • sunitinib • Kadcyla (ado-trastuzumab emtansine) • Balversa (erdafitinib) • Mektovi (binimetinib) • adavosertib (AZD1775) • Truqap (capivasertib) • Aliqopa (copanlisib) • fexagratinib (ABSK091) • sapanisertib (CB-228) • ipatasertib (RG7440) • taselisib (GDC-0032) • omipalisib (GSK2126458) • ulixertinib (BVD-523) • Erivedge (vismodegib) • Trazimera (trastuzumab-qyyp) • Fakzynja (defactinib) • GSK2636771 • Paletan (pertuzumab biosimilar) • relatlimab (BMS-986016) • ABP 206 (nivolumab biosimilar) • Pertuvia (pertuzumab biosimilar)
    3ms
    Synergistic Anticancer Effects of Fibroblast Growth Factor Receptor Inhibitor and Cannabidiol in Colorectal Cancer. (PubMed, Nutrients)
    The combination of FGFR inhibitors and cannabidiol exhibited a synergistic effect in inducing cell death in colorectal cancer cells, likely through the ER stress pathway. This study supports the potential of combined FGFR inhibitor and CBD therapy as a promising strategy for enhancing anticancer effects in CRC.
    Journal
    |
    FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor) • ANXA5 (Annexin A5)
    |
    fexagratinib (ABSK091)
    4ms
    Targeting p-FGFR1Y654 Enhances CD8+ T Cells Infiltration and Overcomes Immunotherapy Resistance in Esophageal Squamous Cell Carcinoma by Regulating the CXCL8-CXCR2 Axis. (PubMed, Biomedicines)
    AZD4547, combined with immunotherapy, further promotes immunotherapeutic efficacy in ESCC. In conclusion, our study presents a promising model for combination therapy in ESCC immunotherapy.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
    |
    fexagratinib (ABSK091)
    4ms
    PANoptosis-driven molecular stratification in esophageal squamous cell carcinoma: A multi-omics prognostic model and FGFR-Targeted therapeutic validation. (PubMed, Comput Biol Med)
    This study developed and validated the first prognostic model for ESCC based on PANoptosis, highlighting FGFR inhibitors as potential therapeutic strategies for targeting specific subtypes through the suppression of EMT and modulation of the MYC/E2F pathways.
    Journal
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • FGFR (Fibroblast Growth Factor Receptor) • CCNE1 (Cyclin E1) • CEACAM1 (CEA Cell Adhesion Molecule 1) • CRYAB (Crystallin Alpha B) • PLAU (Plasminogen Activator)
    |
    fexagratinib (ABSK091)
    6ms
    FGFR1 overexpression promotes resistance to PI3K inhibitor alpelisib in luminal breast cancer cells through receptor tyrosine kinase signaling-mediated activation of the estrogen receptor. (PubMed, Cancer Drug Resist)
    Synergistic effects of alpelisib with AZD4547 and fulvestrant were evaluated using the combination index. Our findings establish FGFR1 as a key mediator of alpelisib resistance in ER+ breast cancer. Combining FGFR1 inhibitors with alpelisib-based therapies offers a viable approach for FGFR1-overexpressing tumors.
    Journal
    |
    ER (Estrogen receptor) • FGFR1 (Fibroblast growth factor receptor 1)
    |
    Piqray (alpelisib) • fulvestrant • fexagratinib (ABSK091)
    6ms
    Dysregulated lipids homeostasis disrupts CHAC1-mediated ferroptosis driving fibroblast growth factor receptor tyrosine kinase inhibitor AZD4547 resistance in gastric cancer. (PubMed, Redox Biol)
    Dysregulated lipid homeostasis downregulated CHAC1-mediated ferroptosis, leading to FGFR-TKI resistance in gastric cancer. Overexpression of CHAC1 or inhibiting cholesterol synthesis presents promising therapeutic strategies to overcome FGFR-TKI resistance in GC.
    Journal
    |
    FGFR (Fibroblast Growth Factor Receptor) • CHAC1 (ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1)
    |
    fexagratinib (ABSK091)
    7ms
    National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=423, Active, not recruiting, University of Birmingham | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
    Trial completion date • Trial primary completion date • IO biomarker
    |
    NKX2-1 (NK2 Homeobox 1) • TP63 (Tumor protein 63)
    |
    Xalkori (crizotinib) • Tagrisso (osimertinib) • Ibrance (palbociclib) • Imfinzi (durvalumab) • docetaxel • Koselugo (selumetinib) • Truqap (capivasertib) • fexagratinib (ABSK091) • ceralasertib (AZD6738) • sitravatinib (MGCD516) • vistusertib (AZD2014)