5NQE

Human PARP14 (ARTD8), catalytic fragment in complex with an N-aryl piperazine inhibitor

Summary for 5NQE

• Entry DOI: 10.2210/pdb5nqe/pdb
• Descriptor: Poly [ADP-ribose] polymerase 14, 3-[[4-[4-(4-fluorophenyl)piperazin-1-yl]-4-oxidanylidene-butanoyl]amino]benzamide (3 entities in total)
• Functional Keywords: adp-ribosylation, inhibitor complex, transferase domain, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: Q460N5
• Total number of polymer chains: 2
• Total formula weight: 45034.04

Authors

Karlberg, T.,Thorsell, A.G.,Schuler, H. (deposition date: 2017-04-20, release date: 2017-05-24, Last modification date: 2024-10-23)

Primary citation

Upton, K.,Meyers, M.,Thorsell, A.G.,Karlberg, T.,Holechek, J.,Lease, R.,Schey, G.,Wolf, E.,Lucente, A.,Schuler, H.,Ferraris, D.
Design and synthesis of potent inhibitors of the mono(ADP-ribosyl)transferase, PARP14.
Bioorg. Med. Chem. Lett., 27:2907-2911, 2017

PubMed 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, IC=160nM. 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.

PubMed: 28495083
DOI: 10.1016/j.bmcl.2017.04.089

Experimental method

X-RAY DIFFRACTION (2.71 Å)