MG-V-53 is a potent, high-affinity small-molecule VISTA inhibitor with SPR KD of 106 nM, mimics the interaction of VISTA mAb, has IC50 of 121 nM in FRET assays.
MG-V-53 blocks VISTA-VISTA interaction between Chinese hamster ovary (CHOK1) VISTA cells and Nano-Glo interleukin-2 (IL-2)/Jurkat VISTA cells in a bioluminescent cell-based T cell activation assay.
MG-V-53 selectively reinstates T cell proliferation in the presence of high VISTA-expressing cell lines (OVKATE, SKOV3, COV504, RL952, and HEC1A), while having minimal effect on cancer cell lines exhibiting low VISTA expression (A2780, AN3CA, and Ishikawa).
MG-V-53 up-regulates IFN-γ and TNF-α in supernatants of cocultures of purified human T cells with OVKATE and RL952 cell lines displaying high VISTA expression.
MG-V-53 also shows binding affinity of MG-V-53 to mouse VISTA (MST KD=146 nM).
MG-V-53 (20 mg/kg, p.o.) potentiates the antitumor activity of anti-Programmed Cell Death Ligand 1 (PD-L1) mAb using the MC38 colon cancer model in C57BL/6 mice.