PD-1-IN-1

PD-1-IN-1 is an inhibitor of programmed cell death 1 ligand 1 (PD-L1), PD-L2, and V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA). It rescues PD-L1-, PD-L2-, or VISTA-induced inhibition of IFN-gamma release in isolated human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3 and anti-CD28 antibodies (EC50s = 66.1, 80.9, and 82.9 nM, respectively). PD-1-IN-1 is selective for these immune checkpoint proteins over B7-1 and cytotoxic T lymphocyte protein 4 (CTLA-4) at 1,000 nM and a panel of 80 receptors, transporters, and enzymes at 10,000 nM. It does not induce IL-2, IFN-gamma, or TNF-alpha release in isolated human PBMCs in an in vitro cytokine storm assay when used at concentrations ranging from 10-1,000 nM. PD-1-IN-1 (10 mg/kg, p.o.) increases proliferation and activation of tumor-infiltrating T cells and decreases tumor volume in a CT26 murine colon cancer model. InChI: InChI=1S/C12H20N6O7/c1-4(20)8(11(22)23)16-12(24)15-6(2-7(14)21)10-17-9(18-25-10)5(13)3-19/h4-6,8,19-20H,2-3,13H2,1H3,(H2,14,21)(H,22,23)(H2,15,16,24)/t4-,5+,6+,8+/m1/s1 InChIKey: HFOBENSCBRZVSP-LKXGYXEUSA-N SMILES: O=C(N[C@H](C(O)=O)[C@H](O)C)N[C@H](C1=NC([C@@H](N)CO)=NO1)CC(N)=O