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    1m
    Novel pyrrolone-fused benzosuberene MK2 inhibitors: synthesis, pharmacophore modelling, molecular docking, and anti-cancer efficacy evaluation in HNSCC cells. (PubMed, J Biomol Struct Dyn)
    Moreover, immunofluorescence analysis and western-blot assays potentiated, that selected analogues inhibited the inflammatory cytokine TNF-α induced activation of MK2 on cellular and molecular levels in HNSCC cells. In conclusion, this study presents novel MK2-inhibitors and opens the avenue for further pre-clinical and clinical efficacy evaluation of developed PfBS analogues in the treatment of HNSCC.Communicated by Ramaswamy H. Sarma.
    Journal
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    TNFA (Tumor Necrosis Factor-Alpha)
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    benzosuberene
    almost2years
    Targeting anticancer agents to the tumor microenvironment with cathepsin B cleavable drug-linker conjugates of phosphatidylserine-binding proteins (AACR 2023)
    The payloads include benzosuberene-based aniline KGP156 and its phenolic congener KGP18, dihydronaphthalene-based KGP05, and indole-based OXi8006. Conjugation of thiolated Bavituximab with Mc-Val-Cit-PABC-KGP156 gave a drug/antibody ratio (DAR) of 3.6/1 after cleavage by cathepsin B and determination of released KGP156 by LC-MS. These studies revealed 1) distinct differences in cleavage rates for drug-linkers, 2) cleavage by cathepsin L, and 3) efficient cathepsin B mediated release of payload from the ADC.
    Tarvacin (bavituximab) • benzosuberene • cathepsin L inhibitors