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Showing 1–10 of 10 results
Advanced filters: Author: Jolanta Grembecka Clear advanced filters

  • Fragment screening and medicinal chemistry optimization led to development of a small-molecule inhibitor of RING1B–BMI1 E3 ligase, blocking the H2A ubiquitination activity of the Polycomb repressive complex 1 and inducing differentiation in leukemia cells.

    • Shirish Shukla
    • Weijiang Ying
    • Tomasz Cierpicki
    Research
    Nature Chemical Biology
    Volume: 17, P: 784-793

  • BMI1, a core element of the polycomb repressive complex 1, is suggested to have oncogenic activity in a variety of cancers. Here, the authors report the structure of BMI1 bound to the protein PHC2, identify BMI1 homo-oligomerization interfaces, and analyse the role of BMI1 protein-protein interactions in PRC1 function.

    • Felicia Gray
    • Hyo Je Cho
    • Tomasz Cierpicki
    ResearchOpen Access
    Nature Communications
    Volume: 7, P: 1-12

  • Here, the authors discover that ligandability of BTB domains correlates with the presence of μs-ms time scale dynamics. This finding suggests that protein dynamics may be a broadly applicable tool in drug discovery to assess the ligandability of novel and challenging targets.

    • Vladlena Kharchenko
    • Brian M. Linhares
    • Łukasz Jaremko
    ResearchOpen Access
    Nature Communications
    Volume: 13, P: 1-10

  • The histone methyltransferase ASH1L plays a role in various diseases, including cancer, and has been validated as a therapeutic target; however, no inhibitors of ASH1L have been reported. Here the authors present small molecule inhibitors of ASH1L and demonstrate their on-target activity in leukemia cells and a mouse model of leukemia.

    • David S. Rogawski
    • Jing Deng
    • Jolanta Grembecka
    ResearchOpen Access
    Nature Communications
    Volume: 12, P: 1-14

  • An irreversible small-molecule inhibitor of histone methyltransferase NSD1 is developed, which binds covalently to the C2062 residue in the catalytic SET domain and represses H3K36 dimethylation and target gene expression in leukemia cells.

    • Huang Huang
    • Christina A. Howard
    • Tomasz Cierpicki
    Research
    Nature Chemical Biology
    Volume: 16, P: 1403-1410

  • MLL fusions are linked to leukemias and retain the CXXC domain, which binds unmethylated DNA. The NMR structure of CXXC–DNA now indicates the interactions underlying binding. Mutation of a key residue to a nonbinding form decreases proliferation caused by an MLL-AF9 fusion and leukemias induced by MLL-AF9 expression in mice.

    • Tomasz Cierpicki
    • Laurie E Risner
    • John H Bushweller
    Research
    Nature Structural & Molecular Biology
    Volume: 17, P: 62-68

  • MLL fusion genes often encode leukemogenic proteins that depend on interaction with menin, a component of the MLL SET1-like histone methyltransferase complex. MI-2 and MI-3 are the first small molecules that can block menin–MLL fusion protein interaction and their oncogenic effects in cells.

    • Jolanta Grembecka
    • Shihan He
    • Tomasz Cierpicki
    Research
    Nature Chemical Biology
    Volume: 8, P: 277-284