PD-1-PD-L1

PROTAC PD-1/PD-L1 degrader-1 is a bifunctional degrader that targets the PD-1/PD-L1 immune checkpoint interaction by utilizing a Cereblon E3 ligase ligand. It demonstrates potent inhibitory activity with an IC50 of 39.2 nM, effectively restoring immune function in co-culture models involving liver cancer cells and CD3 T cells. Additionally, this compound reduces PD-L1 protein levels through a lysosome-dependent degradation pathway, making it a valuable tool for research in cancer immunotherapy and immune modulation.

PD-1/PD-L1-IN-54 is an inhibitor of the PD-1/PD-L1 interaction, targeting immune checkpoints critical for tumor immune evasion. With a KD of 55.8 μM for PD-1 and 46.4 μM for PD-L1, and an IC50 of 88.6 μM, this compound enhances CD8+ T cell activation and promotes the secretion of key cytokines such as IFN-γ and IL-2. Furthermore, PD-1/PD-L1-IN-54 exhibits anticancer properties by inhibiting tumor cell proliferation and inducing apoptosis, while also modulating T cell immunity via the PI3K/Akt signaling pathway.

Naamidine J is an imidazole-type alkaloid that functions as a CSE1L/PD-L1 inhibitor. It demonstrates significant anti-inflammatory activity by reducing pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, while enhancing the expression of anti-inflammatory markers like CD206 and Arg-1. Additionally, Naamidine J exhibits antitumor properties and alleviates pulmonary tissue edema and inflammatory infiltrates in murine models. This compound is valuable for research focused on the immune microenvironment in the contexts of acute lung injury and cancer.

PD-L1/HDAC6-IN-1 is a dual inhibitor targeting PD-L1 and HDAC6, effectively disrupting the PD-L1/PD-1 interaction with IC50 values of 26.8 nM and 69 nM, respectively. This compound significantly enhances the cytotoxicity of Jurkat T cells against HepG2 cells with an IC50 of 3.4 μM. Additionally, PD-L1/HDAC6-IN-1 demonstrates favorable pharmacokinetics in rat models, achieving a drug exposure level of 871.62 ng·h/mL, and shows promising antitumor efficacy in B16-F10 xenograft models in mice.

PD-L1/HDAC-IN-1 is a dual inhibitor targeting PD-L1, HDAC2, and HDAC3, with IC50 values of 88.10 nM, 27.98 nM, and 14.47 nM, respectively. This compound effectively disrupts the PD-1/PD-L1 interaction and demonstrates minimal cytotoxicity in MCF-7 cells (IC50=19.34 μM). PD-L1/HDAC-IN-1 enhances the expression of PD-L1 and CXCL10, thereby facilitating an anti-tumor immune response through increased T-cell recruitment into the tumor microenvironment (TME). Its unique mechanism positions it as a valuable tool for research in cancer immunotherapy.

PD-1/PD-L1-IN 3 is a macrocyclic peptide that acts as a selective inhibitor of the PD-1/PD-L1 and CD80/PD-L1 interactions. By binding to PD-L1, it effectively disrupts the binding of PD-L1 to PD-1 and CD80, exhibiting IC50 values of 5.60 nM and 7.04 nM, respectively. This compound is valuable for research in various fields, particularly in cancer immunotherapy and the study of infectious diseases.

PD-1/PD-L1-IN-10 is a potent orally active inhibitor of the PD-1/PD-L1 interaction, with an IC50 value of 2.7 nM. This compound exhibits significant anticancer efficacy by blocking the immune checkpoint pathway, thereby enhancing T-cell activation and promoting anti-tumor responses. PD-1/PD-L1-IN-10 is valuable for research in immunotherapy and cancer treatment studies.

CYP51/PD-L1-IN-3 is a dual inhibitor targeting CYP51 and PD-L1, exhibiting potent antifungal activity with IC50 values of 0.205 μM and 0.039 μM, respectively. This compound induces early apoptosis in fungal cells by reducing levels of intracellular IL-2, NLRP3, and NF-κBp65 proteins. Additionally, CYP51/PD-L1-IN-3 causes mitochondrial damage and reactive oxygen species (ROS) accumulation, ultimately resulting in fungal lysis and cell death. This compound serves as a valuable tool for research in fungal infections and immune modulation.

CYP51/PD-L1-IN-2 is a quinazoline compound that functions as a dual inhibitor of CYP51 and PD-L1, exhibiting IC50 values of 0.263 μM and 0.017 μM, respectively. It displays notable antifungal activity by triggering early apoptosis in fungal cells, leading to significant reductions in intracellular IL-2, NLRP3, and NF-κBp65 protein levels. Additionally, CYP51/PD-L1-IN-2 induces mitochondrial damage and reactive oxygen species (ROS) accumulation, culminating in fungal lysis and subsequent cell death. This compound is valuable for research exploring antifungal mechanisms and cancer immunotherapy.

CYP51/PD-L1-IN-1 is a dual inhibitor targeting both CYP51 and PD-L1, exhibiting an IC50 of 0.884 μM for CYP51 and 0.083 μM for PD-L1. This quinazoline compound demonstrates notable antifungal activity by inducing early apoptosis in fungal cells while significantly reducing intracellular levels of IL-2, NLRP3, and NF-κBp65. Additionally, CYP51/PD-L1-IN-1 contributes to mitochondrial damage and reactive oxygen species (ROS) accumulation, ultimately leading to fungal lysis and cell death. This compound is valuable for research focused on antifungal therapies and immune modulation.

Nilvanstomig is an anti-PD-1/TIGIT antibody that targets the PD-1/TIGIT pathway, thereby facilitating T cell activation and enhancing natural killer (NK) cell anti-tumor activity. This compound is particularly relevant in the study of advanced cervical cancer and contributes to research focused on immune modulation and cancer immunotherapy. Its mechanism of action underscores its potential for strengthening anti-tumor responses in various oncological contexts.

Davoceticept is a fusion protein consisting of the CD80 (1-107) fragment linked to IGHG1 Fc via a peptidyl linker, targeting CTLA-4 and PD-L1. This variant CD80 vIgD-Fc acts as an immune checkpoint inhibitor, enhancing T cell activation and promoting anti-tumor responses. Its applications include cancer immunotherapy and studying immune modulation in various malignancies, making it a valuable tool for researchers investigating therapeutic strategies in cancer treatment.