GeA-69 is a selective allosteric inhibitor of macrodomain 2 of poly-adenosine-diphosphate-ribose polymerase 14 (PARP14), an anti-apoptotic pro-survival protein associated with inflammatory diseases and several types of cancer. GeA-69 exhibited a KD of 860 nM in ITC experiments. GeA-69 was shown to be an allosteric inhibitor of adenosine diphosphate ribose (ADPR) binding to PARP14 macrodomain 2 and to prevent recruitment of the PAPP14 macrodomain 2 to DNA damage sites.
Selective allosteric inhibitor of PARP14 macrodomain 2
ACS chemical biology, 12(11), 2866-2874 (2017-10-11)
Macrodomains are conserved protein interaction modules that can be found in all domains of life including in certain viruses. Macrodomains mediate recognition of sequence motifs harboring adenosine diphosphate ribose (ADPR) modifications, thereby regulating a variety of cellular processes. Due to
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