Development and structural analysis of adenosine site binding tankyrase inhibitors.
Oulu, Finland. In Bioorg Med Chem Lett, Feb 2016
The scaffold also enables a fine modulation of selectivity towards either tankyrase 1 or tankyrase 2. In order to get insight about the binding mode of the inhibitors, we solved crystal structures of the compounds in complex with tankyrase 2. The compounds bind to the adenosine pocket of the catalytic domain and cause changes in the protein structure that are modulated by the chemical modifications of the compounds.
Chemical Disruption of Wnt-dependent Cell Fate Decision-making Mechanisms in Cancer and Regenerative Medicine.
Dallas, United States. In Curr Med Chem, 2014
In this review, we will discuss how medicinal chemistry efforts focused on first in class small molecules targeting two Wnt pathway components - the polytopic Porcupine (Porcn) acyltransferase and the cytoplasmic Tankyrase (Tnks) poly-ADP-ribosylases - have contributed to our understanding of the druggable genome and expanded the armamentarium of chemicals that can be used to influence cell fate decision-making.
Recent advances in the structure-based rational design of TNKSIs.
Jinan, China. In Mol Biosyst, 2014
This article provides a fairly comprehensive overview of the structural biology of the TNKS-inhibitor complex and the current medicinal chemistry strategies being used in the structure-based rational design of tankyrase-specific inhibitors.
New PARP targets for cancer therapy.
Cambridge, United States. In Nat Rev Cancer, 2014
The best-studied PARPs generate PAR modifications and include PARP1 and the tankyrase PARP5A, both of which are targets for cancer therapy with inhibitors in either clinical trials or preclinical development.
Tankyrase inhibitors as therapeutic targets for cancer.
Hyderābād, India. In Curr Top Med Chem, 2013
Tankyrase 1 and 2 belonging to the family of poly(ADP-ribosyl)ases play an important role in PARsylation by utilizing NAD+ as a substrate in order to generate ADP-ribose polymers.
Proteasome regulation by ADP-ribosylation.
New York City, United States. In Cell, 2013
We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31.
Tankyrase-targeted therapeutics: expanding opportunities in the PARP family.
London, United Kingdom. In Nat Rev Drug Discov, 2012
Efforts to pharmacologically target PARP enzymes have largely focused on PARP1 and the closely related PARP2, but recent work highlighting the role of another family member, tankyrase 1 (TANK1; also known as PARP5A and ARTD5), in the control of WNT signalling has fuelled interest in the development of additional inhibitors to target this enzyme class.