pd-1/pd-l1 interaction

BMS-202 (PD1-PDL1 inhibitor 2) is an inhibitor of the PD-1 (Programmed death- 1) PD-Ll (Programmed death-ligand 1) protein protein interaction.

BMS-1 (PD-1 PD-L1 inhibitor 1) is an inhibitor of the PD1-PD-L1 protein-protein interaction. It also acts as an immunomodulator. Programmed death ligand 1 (PD-L1) is a protein in humans that is encoded by the CD274 gene and the upregulation of PD-L1 allows Ys to evade the host immune system. High tumor expression of PD-L1 was associated with increased tumor aggressiveness and a 4.5-fold increased risk of death.

Atezolizumab is an antibody inhibitor, a humanized monoclonal antibody, IgG1, which targets PD-L1 and blocks the interaction of PD-L1 with PD-1. Atezolizumab has antitumor activity and promotes T-cells to attack tumor cells.

PD-1-IN-22 is a potent inhibitor of the programmed cell death-1 (PD-1) programmed cell death-ligand 1 (PD-L1) interaction, with an IC50 of 92.3 nM.

BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride, a resorcinol di-Ph ether scaffold-based programmed cell death-1 (PD-1) programmed cell death ligand 1 (PD-L1) inhibitor, inhibits the PD-1 PD-L1 interaction with an IC50 of 39.2 nM. It contains the target protein PD-1 PD-L1 ligand and PROTAC linker, which can be used to synthesize PROTAC PD-1 PD-L1 degrader-1 and has anticancer activity. Additionally, it serves as a diluent for the preparation of tablets for direct compression.

PD-1 PD-L1-IN-9, with an IC50 of 3.8 nM, is a potent and orally active inhibitor of the PD-1 PD-L1 interaction. It enhances the immune cells' ability to kill tumor cells and demonstrates significant antitumor activity in vivo in a CT26 mouse model.

BMS-1001 is a potent inhibitor of PD-1 PD-L1 interaction(IC50 : 2.25 nM, in a homogenous time-resolved fluorescence binding assay).

Durvalumab (MEDI 4736) is a humanized monoclonal antibody targeting PD-L1. It can block the interaction of PD-L1 with PD-1 and CD80, with IC50 values of 0.1 and 0.04 nM, respectively. Durvalumab is often used in combination with platinum-based compounds for the treatment of non-small cell lung cancer and advanced hepatocellular carcinoma cells.

PD-1 PD-L1-IN 5 is an inhibitor of PD-1 PD-L1 protein-protein interaction with an IC50 of ≤100 nM.

Motixafortide (BKT140 4-fluorobenzoyl) is an antagonist of CXCR4 (IC50: 1 nM). BMS-1166 hydrochloride is an inhibitor of PD-1 PD-L1 interaction (IC50: 1.4 nM). BMS-1166 rivalries the inhibitory effect of PD-1 PD-L1 immune checkpoint on T cell activation.

PD-1 PD-L1-IN-51 (Compound III-4) is an inhibitor of PD-1 PD-L1 (IC50: hPD-L1 at 2.9 nM). It binds directly to PD-L1, blocking the interaction between PD-1 and PD-L1, and enhancing the release of IFN-γ. Additionally, PD-1 PD-L1-IN-51 exhibits antitumor activity.

LSD1-IN-35 (Compound Z-1) is a selective inhibitor of LSD1, exhibiting an IC50 of 108 nM. This compound inhibits the demethylation of H3K4me1 2 and acts as an immunomodulator. Additionally, LSD1-IN-35 enhances the responsiveness of gastric cancer cells to T-cell killing by reducing PD-L1 expression, thereby weakening the PD-1 PD-L1 interaction.

PD-1 PD-L1-IN-52 (Compound Ⅲ-5) is an orally active inhibitor of PD-1 PD-L1 interaction, exhibiting an IC50 of 109.9 nM. It demonstrates antitumor activity in a C57BL 6 mouse model of MC38 colon carcinoma cells expressing human PD-1, achieving a tumor growth inhibition (TGI) rate of 49.6%.

PD-L1degrader-2 (Compound B3) is an orally effective AUTAC degrader that degrades PD-L1 via the autophagy-lysosome pathway with a DC50 of 0.5 μM. It inhibits the interaction between PD-1 and PD-L1, with an IC50 of 22.8 nM. PD-L1degrader-2 upregulates the expression of Atg9b, Lamp1, and Mitf, activating the autophagy-lysosome system. It exhibits antitumor activity in the CT26 mouse model.

D5B is an effective and selective PD-L1 inhibitor that has been modified with DBCO. It degrades PD-L1 in 4T1 and B16-F10 tumor cells with EC50 values of 5.4 μM and 6.2 μM, respectively. D5B can block the PD-L1 PD-1 interaction and exhibits antitumor activity.

PD-L1 VISTA-IN-1 (Compound P17) is an orally active dual inhibitor targeting PD-L1 and VISTA. It effectively hinders the PD-1 PD-L1 interaction (IC50: 0.1492 μM) and the VISTA pathway (KD: 0.2723 μM), leading to the reactivation of T cells. Additionally, PD-L1 VISTA-IN-1 exhibits antitumor activity.

PD-L1 HDAC-IN-1 (Compound 14) is an inhibitor of PD-L1 and HDAC, effectively blocking PD-1 PD-L1 interaction as well as HDAC2 and HDAC3 with IC50 values of 88.10, 27.98, and 14.47 nM, respectively. It exhibits mild cytotoxicity in MCF-7 cells (IC50=19.34 μM) and enhances the expression of PD-L1 and CXCL10, promoting antitumor immune responses by recruiting T cell infiltration into the tumor microenvironment (TME).

PD-L1 HDAC6-IN-1 (Compound HP29) is an inhibitor targeting both PD-L1 and HDAC6, effectively disrupting the PD-L1 PD-1 interaction and inhibiting HDAC6 activity, with IC50 values of 26.8 nM and 69 nM, respectively. This compound enhances the cytotoxicity of Jurkat T cells against HepG2 cells, exhibiting an IC50 of 3.4 μM. In rats, PD-L1 HDAC6-IN-1 demonstrates favorable pharmacokinetics, showing a drug exposure level of 871.62 ng·h mL, and displays antitumor activity in a B16-F10 xenograft mouse model.

BMS-242 is an effective inhibitor of PD-1/PD-L1 interaction.

BMS-8 is a novel inhibitor of the PD-1 PD-L1 interaction (IC50: 7.2 μM) by binding directly to PD-L1 and inducing the formation of PD-L1 homodimers.

Sintilimab (IBI308) is a humanized IgG4 monoclonal antibody with significant anti-tumor activity that restores endogenous anti-tumor T-cell responses by binding to PD-1 and thereby blocking the interaction of PD-1 with its ligands (PD-L1 and PL-L2).Sintilimab is used in combination with other compounds for the treatment of classical Hodgkin's lymphoma, non-cellular lung cancer and esophageal cancer. Sintilimab is used in combination with other compounds to treat classical Hodgkin's lymphoma, non-small cell lung cancer and esophageal cancer.

CAY10774 is an inhibitor of the protein-protein interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 (IC50= 15 nM in a homologous time-resolved fret (HTRF) assay).1It increases the activation of Jurkat cells expressing PD-1 in co-culture with artificial antigen-presenting cells (aAPCs) expressing PD-L1 (EC50= 6.6 μM in a reporter assay). CAY10774 increases surface expression of PD-1 on primary human CD4+and CD8+T cells co-cultured with aAPCs. 1.Konieczny, M., Musielak, B., Kocik, J., et al.Di-bromo-based small-molecule inhibitors of the PD-1/PD-L1 immune checkpointJ. Med. Chem.63(19)11271-11285(2020)

LH1306 is an inhibitor of the interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 that has an IC50 value of 25 nM in a homologous time-resolved fluorescence (HTRF) assay.1 It increases the activation of Jurkat cells expressing PD-1 in co-culture with U2OS or CHO cells expressing PD-L1 (EC50s = 334 and 4,214 nM, respectively, in reporter assays). |1. Basu, S., Yang, J., Xu, B., et al. Design, synthesis, evaluation, and structural studies of C2-symmetric small molecule inhibitors of programmed cell death-1/programmed death-ligand 1 protein-protein interaction. J. Med. Chem. 62(15), 7250-7263 (2019).

LH1307 is an inhibitor of the interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 that has an IC50 value of 3 nM in a homologous time-resolved fluorescence (HTRF) assay.1 It increases the activation of Jurkat cells expressing PD-1 in co-culture with U2OS or CHO cells expressing PD-L1 (EC50s = 79 and 763 nM, respectively, in reporter assays). |1. Basu, S., Yang, J., Xu, B., et al. Design, synthesis, evaluation, and structural studies of C2-symmetric small molecule inhibitors of programmed cell death-1/programmed death-ligand 1 protein-protein interaction. J. Med. Chem. 62(15), 7250-7263 (2019).