Skip to content
DraconiticResearch
Search Sources API
181,713 studies31 sourcesUpdated 55 min ago
Peer-reviewedCC BYACS bio & med chem Au

Cellular Morphological Profiling of PROTAC Degraders of the m6A RNA Methyltransferase METTL3.

  • Mao Jiang1,2,3,4
  • Chukwudi T Ugwu4
  • Laura Wortmann1,2,3,4
  • Jeffrey L Schloßhauer1,2,3,4
  • Christian Begemann1,2,3,4
  • Sonja Sievers2,4,5
  • Katarzyna W Kliza4
  • Peng Wu1,2,3,4
5 affiliations
  1. 1Chemical Genomics Centre, Max Planck Institute of Molecular Physiology, Dortmund 44227, Germany.
  2. 2Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund 44227, Germany.
  3. 3Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund 44227, Germany.
  4. 4Max Planck Institute of Molecular Physiology, Dortmund 44227, Germany.
  5. 5Compound Management and Screening Center, Dortmund 44227, Germany.
Read full textPDFDOICite

Abstract

Methylation of N6-adenosine is the most abundant RNA modification, which is mainly installed on mRNA by the methyltransferase METTL3-METTL14 complex. Dysregulation of the catalytic activity of METTL3 has been associated with many human diseases, especially in acute myeloid leukemia and other cancers. Therefore, both monovalent small-molecule inhibitors and bivalent heterobifunctional proteolysis-targeting chimera (PROTAC) degraders have been pursued to address METTL3 for therapeutic development. In this study, we report the structure-based design and synthesis of new METTL3-targeting PROTACs, as well as the first application of unbiased morphological profiling of the obtained METTL3 PROTACs in the cell painting assay to obtain phenotypic characterization data for the further development of METTL3 PROTAC degraders.

Related

  1. Scoring close linker analogues in PROTAC ternary complexes: A matched-pose study of VHL-recruiting SHP2 degraders
    Tasniqul Islam
    ChemRxivPreprintCC BYFull textMolecular biology & gene regulationChemRxiv
  2. High-content morphological profiling by Cell Painting in 3D spheroids
    Christa Ringers, David Holmberg, Anders Larsson +11
    Nature CommunicationsPeer-reviewedCC BY 4.0Full textBiophysicsCrossrefEurope PMC
  3. Multiplexed embryo profiling links cellular state to zygotic genome activation in single cells.
    Max Hess, Marvin F Wyss, Edlyn Wu +8
    Nature communicationsPeer-reviewedCC BYFull text2 citedBiophysicsEurope PMC
  4. Single-cell profiling defines cellular ecosystems and malignant cell state coupling across pan-cancer tumor microenvironments.
    Xiaoxiao Yang, Yang Tong, Yuting Wang +4
    Molecular cancerPeer-reviewedCC BY-NC-NDFull textMolecular biology & gene regulationEurope PMCDOAJ
  5. Sub-stoichiometric degradation is dispensable for potent PROTACs as demonstrated by irreversible covalent BTK degraders
    Ran Cheng, Hanfeng Lin, Xin Yu +5
    Nature CommunicationsPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationCrossref

Cite

BibTeXRIS
BibTeX
@article{jiang2026cellular,
  title = {{Cellular Morphological Profiling of PROTAC Degraders of the m6A RNA Methyltransferase METTL3.}},
  author = {Mao Jiang and Chukwudi T Ugwu and Laura Wortmann and Jeffrey L Schloßhauer and Christian Begemann and Sonja Sievers and Katarzyna W Kliza and Peng Wu},
  journal = {ACS bio \& med chem Au},
  year = {2026},
  month = oct,
  doi = {10.1021/acsbiomedchemau.6c00136},
  url = {https://europepmc.org/article/MED/42921299},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cellular Morphological Profiling of PROTAC Degraders of the m6A RNA Methyltransferase METTL3.
AU  - Mao Jiang
AU  - Chukwudi T Ugwu
AU  - Laura Wortmann
AU  - Jeffrey L Schloßhauer
AU  - Christian Begemann
AU  - Sonja Sievers
AU  - Katarzyna W Kliza
AU  - Peng Wu
PY  - 2026
DA  - 2026/10/06
JO  - ACS bio & med chem Au
DO  - 10.1021/acsbiomedchemau.6c00136
UR  - https://europepmc.org/article/MED/42921299
AB  - Methylation of N6-adenosine is the most abundant RNA modification, which is mainly installed on mRNA by the methyltransferase METTL3-METTL14 complex. Dysregulation of the catalytic activity of METTL3 has been associated with many human diseases, especially in acute myeloid leukemia and other cancers. Therefore, both monovalent small-molecule inhibitors and bivalent heterobifunctional proteolysis-targeting chimera (PROTAC) degraders have been pursued to address METTL3 for therapeutic development. In this study, we report the structure-based design and synthesis of new METTL3-targeting PROTACs, as well as the first application of unbiased morphological profiling of the obtained METTL3 PROTACs in the cell painting assay to obtain phenotypic characterization data for the further development of METTL3 PROTAC degraders.
SN  - 2694-2437
ER  -