anti-tumor immunity

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

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]

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]

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.

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)

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.

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].

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.

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.

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.

5-Hydroxy-L-tryptophan-4,6,7-d3 is L-5-Hydroxytryptophan labeled with 2H. L-5-Hydroxytryptophan (L-5-HTP) is a dietary supplement and a precursor to serotonin, which inhibits the IFN-γ induced PD-L1 expression. It promotes anti-tumor immunity and is used in research on migraine and depression.

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-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.

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.

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-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.

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.