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Identification of a Protein Arginine Methyltransferase 7 (PRMT7)/Protein Arginine Methyltransferase 9 (PRMT9) Inhibitor. 2023
Alessandra Feoli, and
Giulia Iannelli, and
Alessandra Cipriano, and
Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
Department of Pharmacy, Epigenetic Med Chem Lab, University of Salerno, via Giovanni Paolo II 132, Fisciano ,I-84084 SA Italy.
Less studied than the other protein arginine methyltransferase isoforms, PRMT7 and PRMT9 have recently been identified as important therapeutic targets. Yet, most of their biological roles and functions are still to be defined, as well as the structural requirements that could drive the identification of selective modulators of their activity. We recently described the structural requirements that led to the identification of potent and selective PRMT4 inhibitors spanning both the substrate and the cosubstrate pockets. The reanalysis of the data suggested a PRMT7 preferential binding for shorter derivatives and prompted us to extend these structural studies to PRMT9. Here, we report the identification of the first potent PRMT7/9 inhibitor and its binding mode to the two PRMT enzymes. Label-free quantification mass spectrometry confirmed significant inhibition of PRMT activity in cells. We also report the setup of an effective AlphaLISA assay to screen small molecule inhibitors of PRMT9.
Related Publications
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Giulia Iannelli, and
Alessandra Cipriano, and
Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
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Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
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Giuliana Sarno, and
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Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
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Cyrus Safaeipour, and
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Giuliana Sarno, and
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Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
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Life (Basel, Switzerland),
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Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
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Sandro Cosconati, and
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Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
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Zhihao Wang, and
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Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
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The Journal of biological chemistry,
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Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
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The Journal of biological chemistry,
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Alessandra Cipriano, and
Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
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Nature communications,
Alessandra Feoli, and
Giulia Iannelli, and
Alessandra Cipriano, and
Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
January 2023,
PloS one,
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Giulia Iannelli, and
Alessandra Cipriano, and
Ciro Milite, and
Lei Shen, and
Zhihao Wang, and
Andrea Hadjikyriacou, and
Troy L Lowe, and
Cyrus Safaeipour, and
Monica Viviano, and
Giuliana Sarno, and
Elva Morretta, and
Maria Chiara Monti, and
Yanzhong Yang, and
Steven G Clarke, and
Sandro Cosconati, and
Sabrina Castellano, and
Gianluca Sbardella
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