Identification of a novel histone H2A mono-ubiquitination-inhibiting cell-active small molecule

被引：1
作者：
Ni, Siyao [1 ]
Takada, Yuri [1 ]
Ando, Takaaki [1 ]
Yu, Shengwang [1 ]
Yamashita, Yasunobu [1 ]
Takahashi, Yukari [2 ]
Sawada, Miho [1 ]
Oba, Makoto [2 ]
Itoh, Yukihiro [1 ]
Suzuki, Takayoshi [1 ]
机构：
[1] Osaka Univ, SANKEN, 8-1 Mihogaoka, Osaka, Ibaraki 5670047, Japan
[2] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Chem, 1-5 Shimogamohangi Cho,Sakyo ku, Kyoto 6060823, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2024年 / 105卷
关键词：
Epigenetics; PRC1; Histone modification; RING1A/B; PRC1; UBIQUITYLATION; RECRUITMENT; EXPRESSION; RING1A;
D O I：
10.1016/j.bmcl.2024.129759
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Histone H2A mono-ubiquitination plays important roles in epigenetic gene expression and is also involved in tumorigenesis. Small molecules controlling H2A ubiquitination are of interest as potential chemical tools and anticancer drugs. To identify novel small molecule inhibitors of H2A ubiquitination, we synthesized and evaluated several compounds designed based on PRT4165 (1), which is a reported histone ubiquitin ligase RING1A inhibitor. We found that compound 11b strongly inhibited the viability and reduced histone H2A monoubiquitination in human osteosarcoma U2OS cells. Therefore, compound 11b is a promising lead compound for the development of H2A histone ubiquitination-inhibiting small molecules.
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页数：5
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  • [1] Synthesis of spiroindene-1,3-dione isothiazolines via a cascade michael/1,3-dipolar cycloaddition reaction of 1,3,4-oxathiazol-2-one and 2-arylidene-1,3-indandiones
    Aitha, Anjaiah
    Yennam, Satyanarayana
    Behera, Manoranjan
    Anireddy, Jaya Shree
    [J]. TETRAHEDRON LETTERS, 2017, 58 (06) : 578 - 581
  • [2] Disorders of histone methylation: Molecular basis and clinical syndromes
    Al Ojaimi, Mode
    Banimortada, Bashar J.
    Othman, Amna
    Riedhammer, Korbinian M.
    Almannai, Mohammed
    El-Hattab, Ayman W.
    [J]. CLINICAL GENETICS, 2022, 102 (03) : 169 - 181
  • [3] The E3 Ubiquitin-Ligase Bmi1/Ring1A Controls the Proteasomal Degradation of Top2α Cleavage Complex - A Potentially New Drug Target
    Alchanati, Iris
    Teicher, Carmit
    Cohen, Galit
    Shemesh, Vivian
    Barr, Haim M.
    Nakache, Philippe
    Ben-Avraham, Danny
    Idelevich, Anna
    Angel, Itzchak
    Livnah, Nurit
    Tuvia, Shmuel
    Reiss, Yuval
    Taglicht, Daniel
    Erez, Omri
    [J]. PLOS ONE, 2009, 4 (12):
  • [4] RING1A and BMI1 bookmark active genes via ubiquitination of chromatin-associated proteins
    Arora, Mansi
    Packard, Colin Z.
    Banerjee, Tapahsama
    Parvin, Jeffrey D.
    [J]. NUCLEIC ACIDS RESEARCH, 2016, 44 (05) : 2136 - 2144
  • [5] Breakers and amplifiers in chromatin circuitry: acetylation and ubiquitination control the heterochromatin machinery
    Bailey, Luke T.
    Northall, Sarah J.
    Schalch, Thomas
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 2021, 71 : 156 - 163
  • [6] Polycomb group-mediated histone H2A monoubiquitination in epigenome regulation and nuclear processes
    Barbour, Haithem
    Daou, Salima
    Hendzel, Michael
    Affar, El Bachir
    [J]. NATURE COMMUNICATIONS, 2020, 11 (01)
  • [7] PRC1 Catalytic Activity Is Central to Polycomb System Function
    Blackledge, Neil P.
    Fursova, Nadezda A.
    Kelley, Jessica R.
    Huseyin, Miles K.
    Feldmann, Angelika
    Klose, Robert J.
    [J]. MOLECULAR CELL, 2020, 77 (04) : 857 - +
  • [8] Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation
    Blackledge, Neil P.
    Farcas, Anca M.
    Kondo, Takashi
    King, Hamish W.
    McGouran, Joanna F.
    Hanssen, Lars L. P.
    Ito, Shinsuke
    Cooper, Sarah
    Kondo, Kaori
    Koseki, Yoko
    Ishikura, Tomoyuki
    Long, Hannah K.
    Sheahan, Thomas W. p
    Brockdorff, Neil
    Kessler, Benedikt M.
    Koseki, Haruhiko
    Klose, Robert J.
    [J]. CELL, 2014, 157 (06) : 1445 - 1459
  • [9] BAP1 and cancer
    Carbone, Michele
    Yang, Haining
    Pass, Harvey I.
    Krausz, Thomas
    Testa, Joseph R.
    Gaudino, Giovanni
    [J]. NATURE REVIEWS CANCER, 2013, 13 (03) : 153 - 159
  • [10] Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation
    de Napoles, M
    Mermoud, JE
    Wakao, R
    Tang, YA
    Endoh, M
    Appanah, R
    Nesterova, TB
    Silva, J
    Otte, AP
    Vidal, M
    Koseki, H
    Brockdorff, N
    [J]. DEVELOPMENTAL CELL, 2004, 7 (05) : 663 - 676
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