INCB 086550

INCB 086550 is an inhibitor of the protein-protein interaction between programmed cell death 1 (PD-1) and its ligand PD-L1. It inhibits PD-1 binding to PD-L1 in CHO cells expressing human PD-L1 (EC50 = 13.2 nM). INCB 086550 (1 µM) induces dimerization and internalization of PD-L1 in CHO cells expressing human PD-L1. It decreases the levels of unoccupied cell-surface PD-L1 in mouse MBT-2 bladder cancer cells expressing human PD-L1 at low, medium, or high levels (EC50s = 3.7, 0.4, and 0.1 nM, respectively). It prevents PD-1-induced recruitment of Src homology region 2 domain-containing phosphatase (SHP) in a reporter assay using Jurkat T cells co-cultured with U2OS cells expressing human PD-L1 (IC50 = 6.3 nM) and induces activation of nuclear factor of activated T cells (NFAT) in a reporter assay using Jurkat T cells co-cultured with CHO-K1 cells (IC50 = 21.4 nM). In vivo, INCB 086550 (20 or 200 mg/kg per day) reduces tumor volume and intratumoral cell-surface levels of PD-L1, as well as increases CD8+ T cell tumor infiltration, in an MC-38 murine allograft model of colon carcinoma overexpressing human PD-L1 (MC-38-hPD-L1).Formal Name: (3R)-1-[[7-cyano-2-[3'-[[3-[[(3R)-3-hydroxy-1-pyrrolidinyl]methyl]-1,7-naphthyridin-8-yl]amino]-2,2'-dimethyl[1,1'-biphenyl]-3-yl]-5-benzoxazolyl]methyl]-3-pyrrolidinecarboxylic acid. CAS Number: 2230911-59-6. Molecular Formula: C41H39N7O4. Formula Weight: 693.8. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Ethanol: Soluble, Methanol: Soluble, Water: Soluble. SMILES: CC(C(C1=C(C(NC2=NC=CC3=C2N=CC(CN4CC[C@@H](O)C4)=C3)=CC=C1)C)=CC=C5)=C5C6=NC7=CC(CN8C[C@H](C(O)=O)CC8)=CC(C#N)=C7O6. InChi Code: InChI=1S/C41H39N7O4/c1-24-32(5-3-7-34(24)40-46-36-17-26(15-30(18-42)38(36)52-40)20-47-13-10-29(22-47)41(50)51)33-6-4-8-35(25(33)2)45-39-37-28(9-12-43-39)16-27(19-44-37)21-48-14-11-31(49)23-48/h3-9,12,15-17,19,29,31,49H,10-11,13-14,20-23H2,1-2H3,(H,43,45)(H,50,51)/t29-,31-/m1/s1. InChi Key: QARLNMDDSQMINK-BVRKHOPBSA-N.