8r3f
From Proteopedia
C-terminal Rel-homology Domain of NFAT1
Structural highlights
Publication Abstract from PubMedTranscription 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. Ligandability assessment of the C-terminal Rel-homology domain of NFAT1.,Bottcher J, Fuchs JE, Mayer M, Kahmann J, Zak KM, Wunberg T, Woehrle S, Kessler D Arch Pharm (Weinheim). 2024 Jun;357(6):e2300649. doi: 10.1002/ardp.202300649. , Epub 2024 Feb 23. PMID:38396281[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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