PD-L1-IN-1

PD-L1-IN-1, a powerful PD-L1 inhibitor, demonstrated an IC50 of 115 nM. By forming a robust bond with the PD-L1 protein, PD-L1-IN-1 effectively suppressed tumor growth by enhancing the antitumor immune activity of peripheral blood mononuclear cells in co-cultures with PD-L1 expressing cancer cells (PC9 and HCC827 cells). It significantly elevated the release of interferon γ and induced apoptosis in cancer cells, while exhibiting minimal cytotoxicity in healthy cells [1].

PD-1/PD-L1-IN-14 (compound 17) is an inhibitor of PD-1/PD-L1 interaction (IC50=27.8 nM) that promotes PD-L1 dimerization, endocytosis, and degradation.

PD-1/PD-L1-IN-17 (Compound P20) is a potent PD-1/PD-L1 inhibitor (IC50: 26.8 nM) and a promising lead compound for the development of inhibitors of PD-1/PD-L1 interactions, with potential applications in cancer disease research.

PD-1/PD-L1-IN-15 is a potent PD-1/PD-L1 inhibitor (IC50: 60.1 nM) with demonstrated investigational potential for tumor immunotherapy.

PD-1/PD-L1-IN-16, a potent inhibitor of PD-1/PD-L1 (IC50: 53.2 nM), has demonstrated research potential for tumor immunotherapy.

PD-1/PD-L1-IN-13 is a potent immune checkpoint PD-1/PD-L1 inhibitor with an IC50 value of 10.2 nM for PD-1/PD- L1 interaction.PD-1/PD-L1-IN-13 promotes CD8+ T-cell activation and delays tumour growth in a Hepa1-6 homozygous mouse model.

CYP51/PD-L1-IN-1 (compound L11), a quinazoline with antifungal properties, inhibits CYP51 (IC50: 0.884 μM) and PD-L1 (IC50: 0.083 μM), induces early apoptosis in the fungal cell cycle, decreases intracellular IL-2, NLRP3, and NF-κBp65 protein levels, causes mitochondrial damage and ROS accumulation, leading to fungal lysis and cell death [1].

PD-1/PD-L1-IN-10 is an orally available PD-1/PD-L1 inhibitor (IC50 value of 2.7 nM) that shows anti-tumor activity.

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.

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.

Compound LG-12, known chemically as PD-1/PD-L1-IN-50, is an inhibitor of PD-1/PD-L1. It enhances the secretion of IFN-γ, promotes the activation of CD8+ T cells, and activates T cell-mediated anti-tumor immunity.

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-1/PD-L1-IN-53 (compound B3) serves as an inhibitor targeting both the PD-1/PD-L1 and VISTA signaling pathways. It is utilized in cancer research.

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.

PD-L1/LpxC-IN-1 (Compound 12b) is an inhibitor of PD-L1 and LpxC, with IC50 values of 5.2 μM and 0.081 μM, respectively. This compound disrupts bacterial lipopolysaccharide biosynthesis, leading to bacterial cell lysis and death. It effectively inhibits Gram-negative bacteria, exhibiting a minimum inhibitory concentration (MIC) of 0.25-0.5 μg/mL against K. pneumoniae ATCC 13883, E. coli ATCC 8739, S. typhimurium ATCC 14028, and P. aeruginosa ATCC 9027. Additionally, PD-L1/LpxC-IN-1 modulates the immune response by downregulating the expression of inflammatory cytokines IL-2 and IFN-γ, and upregulating CD4+ and CD8+ cells, thus activating the immune system and mitigating excessive inflammatory responses. In a mouse model of K. pneumoniae ATCC 13883 infection, PD-L1/LpxC-IN-1 demonstrated antibacterial activity.

PD-1/PD-L1-IN-49 (compound 1c) is a potent inhibitor of PD-1/PD-L1 with an IC50 of 77 nM. This compound can activate Jurkat T cells and effectively block the PD-1/PD-L1 immune checkpoint.

PD-1/PD-L1-IN-55 (compound D6) is a potent PD-1/PD-L1 inhibitor with an IC50 of 4.8 nM. It enhances IFN-γ secretion and decreases the proportion of late apoptosis due to PD-L1.

PD-1/PD-L1-IN-40 (Compound EP16) is a PD-1/PD-L1 inhibitor. It effectively suppresses the production of exosomal PD-L1 with an IC50 of 0.108 μM. PD-1/PD-L1-IN-40 serves as a lead compound for the elimination of exosomal PD-L1 and is applicable in cancer research.

PD-1/PD-L1-IN-39 (X 14) is an orally active PD-1/PD-L1 inhibitor with an IC50 value of 15.73 nM. It exhibits strong binding affinity to human and mouse PD-L1, with KD values of 14.62 and 392 nM, respectively. PD-1/PD-L1-IN-39 also demonstrates antitumor activity.

PD-1/PD-L1-IN-41 (Compound 5c) is an inhibitor of PD-L1 and PD-1 with an IC50 value of 10.2 nM.

PD-1/PD-L1-IN-44 (Compound 22) selectively inhibits the PD-1/PD-L1 protein with an IC50 of 1.21 nM. In animal models, PD-1/PD-L1-IN-44 effectively suppressed tumor growth and increased CD8+ cell infiltration without exhibiting toxicity.

PD-1/PD-L1-IN-43 (Compound Z13) is a small molecule inhibitor that specifically targets the interaction between PD-1 and PD-L1. It exhibits significant in vivo antitumor activity against B16-F10 melanoma. By disrupting the interaction between PD-1 and PD-L1, PD-1/PD-L1-IN-43 effectively inhibits tumor growth and is applicable in antitumor research.