Ligandability assessment of the C‐terminal Rel‐homology domain of NFAT1

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Abstract: Transcription factors are generally considered challenging, if not “undruggable”, targets but they promise new therapeutic options due to their fundamental involvement in many diseases. In this study, we aim to assess the ligandability of the C‐terminal Rel‐homology domain of nuclear factor of activated T cells 1 (NFAT1), a TF implicated in T‐cell regulation. Using a combination of experimental and computational approaches, we demonstrate that small molecule fragments can indeed bind to this protein domain. The newly identified binder is the first small molecule binder to NFAT1 validated with biophysical methods and an elucidated binding mode by X‐ray crystallography. The reported eutomer/distomer pair provides a strong basis for potential exploration of higher potency binders on the path toward degrader or glue modalities.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Ligandability assessment of the C‐terminal Rel‐homology domain of NFAT1 ; day:23 ; month:02 ; year:2024 ; extent:7
Archiv der Pharmazie ; (23.02.2024) (gesamt 7)

Creator: Böttcher, Jark
Fuchs, Julian E.
Mayer, Moriz
Kahmann, Jan
Zak, Krzysztof M.
Wunberg, Tobias
Woehrle, Simon
Kessler, Dirk

DOI: 10.1002/ardp.202300649

URN: urn:nbn:de:101:1-2024022414014084209159

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 10:50 AM CEST

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Böttcher, Jark
Fuchs, Julian E.
Mayer, Moriz
Kahmann, Jan
Zak, Krzysztof M.
Wunberg, Tobias
Woehrle, Simon
Kessler, Dirk

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Ligandability assessment of the C‐terminal Rel‐homology domain of NFAT1

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Other Objects (12)

Cotranslational folding of HemK C-terminal domain

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The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes

Solution NMR assignment of the C-terminal domain of human chTOG

Detrimental NFKB1 missense variants affecting the Rel-homology domain of p105/p50

Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain

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Detrimental NFKB1 missense variants affecting the Rel-homology domain of p105/p50

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The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes

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