Identification of a small molecule splicing inhibitor targeting UHM domains.
Humans
Hydrophobic and Hydrophilic Interactions
/ drug effects
Magnetic Resonance Spectroscopy
Mass Screening
Molecular Dynamics Simulation
Mutation
/ genetics
Neoplasms
/ drug therapy
Phosphoproteins
/ genetics
Protein Binding
Protein Interaction Domains and Motifs
/ genetics
RNA Splicing
/ drug effects
RNA Splicing Factors
/ genetics
RNA-Binding Proteins
/ genetics
Small Molecule Libraries
/ chemistry
Spliceosomes
/ drug effects
Splicing Factor U2AF
/ genetics
User-Computer Interface
SF3b1
U2AF homology motif
U2AF2
splicing
splicing inhibitor
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
10
07
2021
received:
06
05
2021
accepted:
13
09
2021
pubmed:
15
9
2021
medline:
19
2
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Splicing factor mutations are frequent in myeloid neoplasms, blood cancers, and solid tumors. Cancer cells harboring these mutations present a particular vulnerability to drugs that target splicing factors such as SF3b155 or CAPERα. Still, the arsenal of chemical probes that target the spliceosome is very limited. U2AF homology motifs (UHMs) are common protein interaction domains among splicing factors. They present a hydrophobic pocket ideally suited to anchor small molecules with the aim to inhibit protein-protein interaction. Here, we combined a virtual screening of a small molecules database and an in vitro competition assay and identified a small molecule, we named UHMCP1 that prevents the SF3b155/U2AF
Substances chimiques
HCC1 autoantigen
0
Phosphoproteins
0
RNA Splicing Factors
0
RNA-Binding Proteins
0
SF3B1 protein, human
0
Small Molecule Libraries
0
Splicing Factor U2AF
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
682-698Informations de copyright
© 2021 Federation of European Biochemical Societies.
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