Theoretical models of inhibitory activity for inhibitors of protein–protein interactions: targeting menin–mixed lineage leukemia with small molecules† †Electronic Supplementary Information (ESI) available: Detailed characterization of the compound collection; structural characteristics of the menin–MI-2-2 complex; and additional computational results. See DOI: 10.1039/c7md00170c

Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia.

Menin functions as a critical oncogenic cofactor of mixed lineage leukemia (MLL) fusion proteins in the development of acute leukemias, and inhibition of the menin interaction with MLL fusion proteins represents a very promising strategy to reverse their oncogenic activity. MLL interacts with menin in a bivalent mode involving 2 N-terminal fragments of MLL. In the present study, we reveal the f...

High-Affinity Small-Molecule Inhibitors of the Menin-Mixed Lineage Leukemia (MLL) Interaction Closely Mimic a Natural Protein–Protein Interaction

The protein-protein interaction (PPI) between menin and mixed lineage leukemia (MLL) plays a critical role in acute leukemias, and inhibition of this interaction represents a new potential therapeutic strategy for MLL leukemias. We report development of a novel class of small-molecule inhibitors of the menin-MLL interaction, the hydroxy- and aminomethylpiperidine compounds, which originated fro...

β-Turn mimetic-based stabilizers of protein–protein interactions for the study of the non-canonical roles of leucyl-tRNA synthetase† †Electronic supplementary information (ESI) available: Detailed procedures for synthesis, bioassay, and biophysical experiments, and full characterization data of all new compounds. See DOI: 10.1039/c5sc03493k Click here for additional data file.

Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available: Synthesis details and structural characterization of compounds, X-ray data collection and statistics, supplementary Fig. S1–S6. See DOI: 10.1039/c6md00531d Click here for additional data file.

a Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom b Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, United Kingdom *E-mail: [email protected] *E-mail: [email protected] †Electronic Supplementary Information (ESI) available: Synthesis details and structural characterization of compounds, X-ray data coll...

Pyrimidine-based twisted donor–acceptor delayed fluorescence molecules: a new universal platform for highly efficient blue electroluminescence† †Electronic supplementary information (ESI) available: General methods, synthesis and characterization data for intermediates, additional computational and photophysical data, TGA data, and OLED device characteristics. CCDC 1500786. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc03793c Click here for additional data file. Click here for additional data file.