Preferred Label : TIGIT/PD-L1 Inhibitor AUR-106;
NCIt synonyms : PDL1/TIGIT Inhibitor AUR-106; TIGIT/PDL1 Inhibitor AUR-106;
NCIt definition : An orally bioavailable small molecule inhibitor of the co-inhibitory molecule and
immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor
tyrosine-based inhibitory motif (ITIM) domains (TIGIT) and the immunosuppressive ligand
programmed cell death-1 ligand 1 (PD-L1; PDL1; cluster of differentiation 274; CD274),
with potential immune checkpoint inhibitory and antineoplastic activities. Upon oral
administration, TIGIT/PD-L1 inhibitor AUR-106 simultaneously targets, binds to and
inhibits TIGIT and PD-L1, thereby inhibiting their downstream signaling pathways.
Inhibition of TIGIT, which is expressed on various immune cells and particularly on
tumor-infiltrating lymphocytes (TILs), prevents the interaction of TIGIT with its
ligands CD112 (nectin-2; poliovirus receptor related-2; PRR2; PVRL2) and CD155 (poliovirus
receptor; PVR; nectin-like protein 5; NECL-5). This enhances the interaction of CD112
and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1),
which is expressed on immune cells, such as natural killer (NK) cells and CD8 T-cells.
This leads to CD226 dimerization and CD226-mediated signaling and activates the immune
system to exert a T-cell-mediated immune response against cancer cells. Inhibition
of PD-L1 prevents its binding to and activation of its receptor, programmed cell death
1 (PD-1; PDCD1; CD279; programmed death-1). This abrogates T-cell inhibition, activates
antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis,
which may lead to a reduction in tumor growth. TIGIT, a member of the Ig super family
(IgSF) and an immune inhibitory receptor, plays a key role in the suppression of T-cell
proliferation and activation; it is involved in tumor cell immune evasion. PD-L1 binding
to PD-1 on activated T-cells inhibits the expansion and survival of CD8-positive T-cells,
suppresses the immune system and results in immune evasion.;
Molecule name : AUR-106; AUR 106;
NCI Metathesaurus CUI : CL1915114;
Origin ID : C200835;
UMLS CUI : C5854613;
Semantic type(s)
- concept_is_in_subset
