NCIt definition : An orally bioavailable second-generation inhibitor of the nuclear enzymes poly(ADP-ribose)
polymerase (PARP) type 1 (PARP1) and 2 (PARP2) and tankyrase (TNK; TNKS; TANK) 1 and
2, with potential chemo/radiosensitizing and antineoplastic activities. Upon oral
administration, nesuparib selectively and simultaneously targets and binds to PARP1/2
and TNK1/2. Inhibiting PARP activity prevents PARP-mediated DNA repair of single-strand
DNA breaks via the base-excision repair pathway. This enhances the accumulation of
DNA strand breaks and promotes genomic instability and eventually leads to apoptosis.
This may enhance the cytotoxicity of DNA-damaging agents. Inhibiting TNK activity
blocks the tankyrase-mediated poly(ADP-ribosyl)ation of multiple target proteins including
various tumor suppressors. This may include the blockage of the poly(ADP-ribosyl)ation
and destabilization of AXIN, a negative regulator of beta-catenin, thereby stabilizing
AXIN. This prevents Wnt/beta-catenin signaling and may inhibit the activation of transcription
of a wide range of Wnt/beta-catenin target genes. This may suppress proliferation
of cancer cells in which Wnt/beta-catenin signaling is overactivated. PARP catalyzes
post-translational ADP-ribosylation of nuclear proteins that signal and recruit other
proteins to repair damaged DNA and is activated by single-strand DNA breaks. The PARP-mediated
repair pathway is dysregulated in a variety of cancer cell types. TNK, a member of
the PARP family, plays an important role in the regulation of the Wnt/beta-catenin
signaling pathway.;
UNII : U6N7333GDW;
CAS number : 2055357-64-5;
Molecule name : JPI-547; JPI 547; NOV 1402; NOV140201;
Semantic type(s)