Design and synthesis of potent inhibitors of the mono(ADP-ribosyl)transferase,PARP14 |
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| Authors: | Kristen Upton Matthew Meyers Ann-Gerd Thorsell Tobias Karlberg Jacob Holechek Robert Lease Garrett Schey Emily Wolf Adrianna Lucente Herwig Schüler Dana Ferraris |
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| Affiliation: | 1. McDaniel College, 2 College Hill, Westminster, MD 21157, United States;2. Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, S-17177 Stockholm, Sweden;3. Stevenson University, 1525 Greenspring Valley Rd, Stevenson, MD 21153, United States |
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| Abstract: | A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were synthesized and tested for their ability to inhibit the mono-(ADP-ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were established for this series and several compounds were identified as sub-micromolar inhibitors of PARP14, the most potent of which was compound 4t, IC50 = 160 nM. Furthermore, profiling other members of this series identified compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity over PARP10, a closely related mono-(ADP-ribosyl)transferase. |
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| Keywords: | PARP PARP14 ARTD-8 Mono(ADP-ribosyl) transferase |
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