anti-tumor immunity

ODM-203, a Selective Inhibitor of FGFR and VEGFR, Shows Strong Antitumor Activity, and Induces Antitumor Immunity

Osunprotafib (ABBV-CLS-484) is a potent, orally bioavailable PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. [1] Osunprotafib (ABBV-CLS-484) stimulates the tumor microenvironment and promotes natural killer cell and CD8 T cell function and enhances T cell anti-tumor immunity by enhancing JAK-STAT signaling and reducing T cell dysfunction. [2]

Dazostinag disodium (TAK-676) is a synthetic novel interferon gene (STING) agonist that triggers STING signaling pathway activation and type I interferon activation. Dazostinag disodium (TAK-676) is also a highly effective immune system modulator with complete resolution and lasting memory of T cell immunity and the ability to promote lasting interferon-dependent anti-tumor immune responses.

MSA-2 is an orally available non-nucleotide STING agonist. The non-covalent dimer of MSA-2 binds to STING with nanomolar affinity. It shows anti-tumor activity in syngeneic mouse tumor models, synergizes with anti-PD-1, stimulates tumor secretion of interferon-β, induces tumor regression, and has long-lasting anti-tumor immunity. [3]

S-Allylmercaptocysteine (SAMC) is an organic sulfur compound extracted from garlic, with anti-cancer, anti-inflammatory, and antioxidant properties. It protects against hepatocellular damage, improves alcoholic liver disease by modulating insulin receptor signaling, and enhances anti-tumor immunity by inhibiting PD-L1 expression.

HDAC8-IN-12 (compound 5k), a non-hydroxamic acid derivative, serves as a selective HDAC8 inhibitor with an IC 50 of 0.12 nM and demonstrates potent efficacy against breast cancer. This compound enhances anti-tumor immunity by activating T cells, elevating M1 macrophage levels, and reducing M2 macrophage proportions. In an orthotopic mouse model of breast cancer, HDAC8-IN-12, administered at 50 mg/kg, effectively suppresses tumor growth.

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.

STINGagonist-45 is a selective STING agonist (EC50= 0.28 μM) that activates the innate immune response through the cGAS-STING pathway, increasing key markers such as p-TBK1 and IRF3. This compound exhibits potent STING activation in human peripheral blood mononuclear cells (PBMC), inducing type I interferons like IFN-β and downstream cytokines such as TNF-α and IL-6. In mouse models, STINGagonist-45 enhances anti-tumor immunity, inhibits tumor growth, and increases CD8+ T cell infiltration. It is applicable for research on STING-associated diseases.

DGKα/ζ-IN-2 is a potent, orally active, and highly selective inhibitor of DGKα/ζ, exhibiting IC50 values of 23 nM for DGKα and 1.2 nM for DGKζ. It shows excellent selectivity over other DGK isoforms such as DGKβ and DGKγ. In the OT-1 mouse model, DGKα/ζ-IN-2 demonstrates significant and dose-dependent immune activation under antigen-presenting conditions. This compound can be utilized in research related to anti-tumor immunity.

CD28-IN-2 is a selective inhibitor of the CD28-B7 interaction (IC50: 22.4 μM) that directly binds to CD28, with a Kd value of 24.1 μM. It inhibits CD28-driven immune activation and blocks T cell costimulation. CD28-IN-2 is applicable in the research of anti-tumor immunity and immune-related diseases.

Adenosine 5'-methylenediphosphate is an inhibitor of ecto-5'-nucleotidase, also known as CD73, with a Kivalue of 37 nM.1It inhibits cAMP accumulation induced by adenosine 5'-monophosphate , adenosine 5'-diphosphate , or adenosine 5'-triphosphate but not adenosine in VA-13 human fibroblasts when used at a concentration of 100 μM. Adenosine 5'-methylenediphosphate reduces proliferation of U138MG glioma cells, as well as inhibits the invasion and migration of MHCC97H hepatocellular carcinoma (HCC) cells in a migration assay.2,3It increases tumor infiltration of CD3+CD8+T cells and reduces tumor growth in a K1735 murine melanoma model when administered at a dose of 400 μg/mouse.4 1.Bruns, R.F.Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosineNaunyn Schmiedebergs Arch. Pharmacol.315(1)5-13(1980) 2.Braganhol, E., Tamajusuku, A.S.K., Bernardi, A., et al.Ecto-5′-nucleotidase/CD73 inhibition by quercetin in the human U138MG glioma cell lineBiochim. Biophys. Acta1770(9)1352-1359(2007) 3.Shali, S., Yu, J., Zhang, X., et al.Ecto\5′\nucleotidase (CD73) is a potential target of hepatocellular carcinomaJ. Cell Physiol.234(7)10248-10259(2018) 4.Forte, G., Sorrentino, R., Montinaro, A., et al.Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanomaJ. Immunol.189(5)2226-2233(2021)

1. (20R)-Protopanaxadiol ((20R)-Protopanaxdiol) has the effect of anti-tumor through increasing the activity of body immunity, inhibiting tumor interstitial microvascular density and its proliferation activity, improving the lymphocyte transformation, the activity of NK cells and the contents of IL-2 significantly. 2. (20R)-Protopanaxadiol prevents and heals obesity, fatty liver and hypertriglyceridemia in mice fed with a high-fat diet.

HDAC-IN-32 is a highly effective HDAC inhibitor presenting IC50 values of 5.2, 11, and 28 nM for HDAC1, HDAC2, and HDAC6, respectively. This compound demonstrates notable anti-proliferative properties against tumor cells, as well as significant in vivo antitumor efficacy, which can elicit antitumor immunity [1].

HPK1-IN-29 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1), a negative regulator of the activation response of dendritic cells (DCs), T cells, and B cells. HPK1-IN-29 enhances anti-tumor immunity in humans and shows potential for studying immune-related diseases, particularly tumors.

PD-1/PD-L1-IN-25, an inhibitor of PD-1/PD-L1 interaction (IC50: 16.17 nM), effectively activates anti-tumor immunity in T cells within PBMCs and can be utilized in cancer research.

HPK1-IN-28, a potent inhibitor of HPK1, enhances anti-tumor immunity in humans and demonstrates research potential in immune-related diseases, particularly tumors, by acting as a negative regulator of dendritic cell (DC), T-cell, and B-cell activation responses.

Finotonlimab is a highly specialized recombinant humanized monoclonal antibody of the immunoglobulin G4 isotype target the human programmed cell death protein 1 receptor with exceptional binding affinity and selectivity, restoration of T-lymphocyte mediated anti-tumor immunity by disrupting the inhibitory signaling axis established through interactions with PD-L1 and PD-L2 ligands across various preclinical and clinical experimental models of advanced solid malignancies.

Bavituximab (Anti-Human Phosphatidylserine Recombinant Antibody) is a monoclonal antibody targeting phosphatidylserine (PS) with vascular targeting and immunomodulatory properties, capable of reactivating anti-tumor immunity to inhibit tumor growth. It has anti-cancer activity and is frequently used with Paclitaxel and Carboplatin in non-small cell lung cancer studies.

Alsevalimab (FPA-150) is a humanized monoclonal antibody that targets B7-H4. Alsevalimab specifically binds to B7-H4 on the surface of tumor and immune cells, blocking its inhibitory signals on T-cell activation, reversing the immunosuppressive state of the tumor microenvironment, and activating the proliferation and tumor-killing functions of effector T cells. Alsevalimab also mediates ADCC effects, synergistically enhancing antitumor immunity. Alsevalimab is suitable for use in studies of solid tumors.

Lesabelimab is an immunoglobulin anti-CD274 monoclonal antibody. As an immune checkpoint ligand, CD274 inhibits the body's anti-tumor immune response by binding to the PDCD1 receptor.

LYP-IN-4 (compound D14), a reversible and selective lymphotyrosine phosphatase (LYP) inhibitor (Ki=1.34 μM, IC50=3.52μM), regulates TCR signaling, increases PD-1/PD-L1 expression, and strengthens anti-tumor immunity. It also stimulates T cell activation, impedes M2 macrophage polarization, and suppresses tumor progression in MC38 isogenic mouse models.

Sasanlimab represents a highly specialized humanized IgG4 monoclonal antibody specifically engineered to target the human programmed cell death protein 1 (PD-1) with exceptional binding affinity. It effectively facilitates the measurable blockade of the PD-1/PD-L1 and PD-1/PD-L2 inhibitory axes across various preclinical experimental models to evaluate the restoration of T-cell mediated anti-tumor immunity and the reversal of immune exhaustion during strictly monitored laboratory observation periods.

Iso5-2DC18, a lipid, is utilized in the synthesis of amine-containing lipids, which are instrumental in mRNA delivery, activation of the stimulator of interferon genes (STING) pathway, and demonstration of anti-tumor immunity [1].

SX-682 is an orally available allosteric inhibitor of CXCR1 and CXCR2 that blocks tumor myeloid suppressor cell recruitment and enhances T cell activation and anti-tumor immunity, with the potential to treat castration-resistant prostate cancer.