Preferred Label : Pan-DDR DNA Decoy-cholesterol Conjugate VIO-01;
NCIt synonyms : Pan-DDR DNA Decoy Oligodeoxynucleotide VIO-01; Pan-DDR DNA Decoy Oligonucleotide VIO-01; Pan-DDR DNA Decoy ODN VIO-01;
NCIt definition : A pan-DNA damage response (DDR) DNA decoy linked to a cholesterol molecule, with potential
immunomodulatory and antineoplastic activities. Upon administration of pan-DDR DNA
decoy-cholesterol conjugate VIO-01, the cholesterol moiety enables tumoral and nuclear
uptake of the DNA, and mimics DNA double-strand breaks (DSBs) inside the tumor cells.
This triggers false DNA break signals, binding to and activating DNA repair proteins
including poly(ADP-ribose) polymerase (PARP) 1, KU70/80, MRN complex and MSH2/MSH3.
This prevents the recruitment of these repair proteins at the actual damage site and
inhibits various DNA DSB repair pathways. This promotes genetic instability and enhances
the accumulation of single and double strand DNA breaks, ultimately leading to apoptosis
of tumor cells. VIO-01 also triggers the activation of the stimulator of interferon
genes protein (STING; transmembrane protein 173; TMEM173) pathway in immune cells
in the tumor microenvironment (TME). This leads to the production of pro-inflammatory
cytokines, including interferons (IFNs), enhances the cross-presentation of tumor-associated
antigens (TAAs) by dendritic cells (DCs), and induces a cytotoxic T-lymphocyte (CTL)-mediated
immune response against cancer cells. PARP1 catalyzes post-translational ADP-ribosylation
of nuclear proteins that signal and recruit other proteins to repair damaged DNA and
plays a key role in the repair of single strand DNA (ssDNA) breaks and DSBs. STING,
a transmembrane protein that activates immune cells in the TME, plays a key role in
the activation of the innate immune system.;
Molecule name : VIO 01; VIO-01; OX-425; OX 425;
NCI Metathesaurus CUI : CL1928802;
Origin ID : C206712;
concept_is_in_subset
