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    DRUG:

    GS-626510

    i
    Other names: GS-626510, GS 626510, GS-6510
    Company:
    Gilead
    Drug class:
    BET inhibitor, BRD4 inhibitor
    Related drugs:
    over2years
    The synergistic interaction of the BET antagonist GS-626510 with the PI3Kδ inhibitor idelalisib in diffuse large B-cell lymphoma involves the blockade of the tumor-macrophage crosstalk (EACR 2022)
    In vivo, when compared to idelalisib and GS-626510 single agents, the combo treatment arm underwent a 2-3 fold increase in relative tumor growth inhibition, reaching 85% after two weeks of daily dosing of the animals, with no detectable toxicity. Conclusion The combination of idelalisib and GS-626510 is able to disrupt GCB-DLBCL crosstalk with M2-macrophages, thereby modulating the secretion of several inflammatory cytokines involved in the regulation of tumor B cell apoptotic threshold.
    IO biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • IL10 (Interleukin 10) • IL1RN (Interleukin 1 receptor antagonist)
    |
    Zydelig (idelalisib) • GS-626510
    over3years
    Integrated mutational landscape analysis of uterine leiomyosarcomas. (PubMed, Proc Natl Acad Sci U S A)
    Finally, we found olaparib (PARPi; P = 0.002), GS-626510 (C-MYC/BETi; P < 0.000001 and P = 0.0005), and copanlisib (PIK3CAi; P = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.
    Journal • PARP Biomarker
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • DAXX (Death-domain associated protein) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
    |
    TP53 mutation • PTEN mutation • DDR • ALK fusion
    |
    Lynparza (olaparib) • Aliqopa (copanlisib) • GS-626510
    over4years
    Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma. (PubMed, Gynecol Oncol)
    Downregulation/inactivation of HUWE1 may increase c-MYC expression and proliferation in primary-CC-cell-lines. GS-626510 may represent a novel, potentially highly effective therapeutic agent against CC overexpressing c-MYC and/or harboring HUWE1 mutations. Clinical studies with BET inhibitor in CC-patients harboring radiation/chemotherapy-resistant disease are warranted.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HUWE1 (HECT UBA And WWE Domain Containing E3 Ubiquitin Protein Ligase 1)
    |
    MYC amplification • MYC overexpression • MYC expression • HUWE1 mutation
    |
    GS-626510