Structural highlights
Function
[PAR14_HUMAN] Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity.
Publication Abstract from PubMed
A series of diaryl ethers were designed and synthesized to discern the structure activity relationships against the two closely related mono-(ADP-ribosyl)transferases PARP10 and PARP14. Structure activity studies identified 8b as a sub-micromolar inhibitor of PARP10 with approximately 15-fold selectivity over PARP14. In addition, 8k and 8m were discovered to have sub-micromolar potency against PARP14 and demonstrated moderate selectivity over PARP10. A crystal structure of the complex of PARP14 and 8b shows binding of the compound in a novel hydrophobic pocket and explains both potency and selectivity over other PARP family members. In addition, 8b, 8k and 8m also demonstrate selectivity over PARP1. Together, this study identified novel, potent and metabolically stable derivatives to use as chemical probes for these biologically interesting therapeutic targets.
Design, synthesis and evaluation of potent and selective inhibitors of mono-(ADP-ribosyl)transferases PARP10 and PARP14.,Holechek J, Lease R, Thorsell AG, Karlberg T, McCadden C, Grant R, Keen A, Callahan E, Schuler H, Ferraris D Bioorg Med Chem Lett. 2018 Jun 15;28(11):2050-2054. doi:, 10.1016/j.bmcl.2018.04.056. Epub 2018 May 3. PMID:29748053[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Holechek J, Lease R, Thorsell AG, Karlberg T, McCadden C, Grant R, Keen A, Callahan E, Schuler H, Ferraris D. Design, synthesis and evaluation of potent and selective inhibitors of mono-(ADP-ribosyl)transferases PARP10 and PARP14. Bioorg Med Chem Lett. 2018 Jun 15;28(11):2050-2054. doi:, 10.1016/j.bmcl.2018.04.056. Epub 2018 May 3. PMID:29748053 doi:http://dx.doi.org/10.1016/j.bmcl.2018.04.056
