cell infiltration

HCH6-1 is a competitive Formyl peptide receptor 1 (FPR1) antagonist.

Oglemilast (GRC 3886) suppresses pulmonary cell infiltration, including eosinophilia and neutrophilia in vitro and in vivo. Oglemilast is an effective and orally active phosphodiesterase-4 (PDE4) inhibitor (IC50: 0.5 nM for PDE4D3). Oglemilast has the potential for inflammatory airway diseases.

LJP-1586 HCl, a highly selective inhibitor of vascular adhesion protein-1 (VAP-1), exhibits antiinflammation effect by reducing adhesion molecule expression and immune cell infiltration after intracerebral hemorrhage (ICH).

Mepivacaine hydrochloride (Mepivacaine HCl) is the hydrochloride salt form of mepivacaine, an amide derivative with local anesthetic properties.

RO7567132 (FAP-LTBR) is a novel bispecific antibody that binds and agonizes LTBR bivalently while binds and antagonizes FAP monovalently, thereby limiting the activation of LTBR to the tumor microenvironment, inducing the formation of local tertiary lymphoid structures (TLS), and reducing systemic toxicity. Its mouse alternative can inhibit breast cancer growth, and the effect is better when combined with atezolizumab. In the mouse colorectal cancer model, it can also enhance immune cell infiltration and TLS-like structure formation.

Resolvin E1 (RvE1) is an endogenous lipid mediator derived from the omega-3 fatty acid eicosapentaenoic acid (EPA). It exhibits anti-inflammatory properties, activates inflammation resolution, and promotes phagocytic clearance. It prevents 2,4,6-trinitrobenzenesulfonic acid-induced colitis and improves erythrocytosis and severe aplastic anaemia (SAA).

Betamethasone 17-Propionate is a compound used in the study of its effects on endotoxin-induced uveitis in rats, capable of inhibiting cellular infiltration into the aqueous humor when administered topically or systemically at certain doses. However, compared to some other compounds, its inhibitory effects are relatively weaker. When administered systemically, the dosage is 1mg/kg. Additionally, in in vitro interleukin-8 (IL-8) release assays, Betamethasone 17-Propionate's suppression of IL-8 release from rat peritoneal exudate cells is less effective than that of betamethasone. Moreover, the concurrent addition of betamethasone dipropionate with Betamethasone 17-Propionate reduces the suppressive effects of betamethasone on cell infiltration and IL-1β gene expression.

Apilimod (STA 5326) inhibits the production of IL-12 and IL-23 and reduces dendritic cell infiltration in psoriasis.

EP4 receptor antagonist 7 (Compound 14) is an antagonist of the prostaglandin E2 (PGE2) receptor subtype EP4, with an IC50 of 1.1 nM. This compound inhibits PGE2-induced β-arrestin recruitment in HEK293 cells with an IC50 of 0.9 nM. In RAW 264.7 macrophages, it reduces the expression of PGE2-induced IL-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C motif) ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase 1 (Arg1) mRNA. In the CT26 mouse colon cancer model, EP4 receptor antagonist 7, combined with an anti-PD-1 antibody, inhibits tumor growth and enhances CD8+ T cell infiltration into the tumor.

Enpp-1-IN-25 (Compound 30) is an ENPP1 inhibitor with an IC50 of 8.05 nM and exhibits low oral bioavailability. By inhibiting cGAMP degradation, it effectively activates the intracellular STING pathway. Enpp-1-IN-25 can enhance immune cell infiltration and type I interferon response in the tumor microenvironment, thereby increasing the antitumor efficacy of anti-PD-L1 antibodies. It is applicable for research in cancer immunotherapy.

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).

Tubulin polymerization/V-ATPase-IN-1 (compound F10) is an inhibitor of tubulin polymerization and V-ATPase. It exhibits potent antiproliferative activity against four types of human cancer cells by inhibiting both tubulin and V-ATPase. The compound also induces apoptosis and immunogenic cell death while suppressing tumor growth in the RM-1 allograft model with enhanced T lymphocyte infiltration.

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.

ZG-126 is an agonist of the vitamin D receptor (VDR) and an inhibitor of histone deacetylase (HDAC) with an IC50 range of 0.63-67.6 μM. It demonstrates cytotoxicity in cancer cell lines MDA-MB-231 and 4T1. In mouse models, ZG-126 exhibits antitumor and antimetastatic effects against melanoma and triple-negative breast cancer (TNBC). Additionally, it shows anti-inflammatory activity by reducing macrophage infiltration and polarization to the immunosuppressive M2 subtype.

ITK-IN-6 is a potent and selective ITK inhibitor (Kd = 387 nM). It binds directly to the ITK kinase domain. This compound prevents the release of pro-inflammatory cytokines and the activation and differentiation of Th2 and Th17 cells. ITK-IN-6 improves asthma progression by reducing inflammatory cell infiltration, mucus production, and IgE generation. It significantly inhibits airway inflammation and is used in asthma research.

(GalNAc)3-CPT is a glycan-conjugated prodrug that targets the asialoglycoprotein receptor (ASGR) overexpressed on liver cells. It demonstrates significant antitumor activity by activating the cGAS-STING pathway and promoting CD8+ T cell infiltration into tumor sites, leading to apoptosis of tumor cells. In HepG2 cells, it shows an IC50 value of 3.07 μM.

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)

Eleutheroside E has anti-inflammatory effects by inhibiting NF-κB activities. Eleutheroside E significantly decreases the inflammatory cell infiltration, pannus formation, cartilage damage, bone erosion of CIA mice, the generation of TNF-α and IL-6, the m

Betamethasone 21-phosphate is a synthetic glucocorticoid.1It prevents increases in macrophage and eosinophil numbers in bronchoalveolar lavage fluid (BALF) and decreases in blood leukocyte numbers in a guinea pig model of parainfluenza-3 viral infection when administered at a dose of 8 mg/kg but does not prevent airway hyperresponsiveness after infection.2Betamethasone 21-phosphate inhibits cell infiltration into the aqueous humor in a rat model of endotoxin-induced uveitis when administered topically or subcutaneously at doses of 0.01-1% or 1 mg/kg, respectively.3It increases maximal lung pressure volume curves in fetal sheep when administered to pregnant ewes at 0.75 gestation at doses of 80 and 170 μg/kg.1Betamethasone 21-phosphate increases body weight, impairs learning and memory, increases anxiolytic behavior, and reduces hippocampal neurogenesis in CD-1 mice but reduces body weight and increases neurogenesis with no effect on anxiety in high-anxiety DBA/2 mice when administered at a dose of approximately 25 mg/kg per day in the drinking water for seven weeks.4Formulations containing betamethasone 12-phosphate and betamethasone acetate have been used in the treatment of severe allergic conditions and a variety of immune-related conditions. 1.Loehle, M., Schwab, M., Kadner, S., et al.Dose-response effects of betamethasone on maturation of the fetal sheep lungAm. J. Obstet. Gynecol.202(2)186.e181-186.e187(2010) 2.Leusink-Muis, A., Ten Broeke, R., Folkerts, G., et al.Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigsClin. Exp. Allergy29(Suppl. 2)82-85(1999) 3.Tsuji, F., Sawa, K., Kato, M., et al.The effects of betamethasone derivatives on endotoxin-induced uveitis in ratExp. Eye Res.64(1)31-36(1997) 4.Aiello, R., Crupi, R., Leo, A., et al.Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesisBehav. Brain Res.278155-166(2015)

Milategrast is a chemical compound that functions as a potent cell adhesion inhibitor and cell infiltration inhibitor. In vitro studies have demonstrated its ability to effectively inhibit the adhesion of Jurkat cells to human fibronectin, with an IC50 value of less than 5 μM.

SSAO/VAP-1 Inhibitor 1 is a potent compound aimed at inhibiting SSAO/VAP-1, a protein involved in facilitating the translocation of Glucose Transport 4 (GLUT 4) to the cell membrane in adipocytes, thus playing a crucial role in glucose regulation. Additionally, in endothelial cells, this enzyme is responsible for mediating the adherence and infiltration of leukocytes, contributing to inflammatory responses. Given these mechanisms, SSAO/VAP-1 Inhibitor 1 holds considerable potential for research into treatments for inflammation, inflammation-related conditions, diabetes, and diabetes-associated diseases[1].

XT2 is a highly potent, orally active, and selective inhibitor of NF-κB-inducing kinase (NIK), exhibiting an IC50 of 9.1 nM. It effectively suppresses the upregulation of ALT, a vital biomarker for acute liver injury, induced by CCl4. Additionally, XT2 significantly decreases immune cell infiltration into the damaged liver tissue. As a result, XT2 holds immense potential in liver inflammatory disease research [1].

Anti-inflammatory agent 21 (compound 9o) is a low cytotoxic, orally active anti-inflammatory agent that targets NO (IC50: 0.76 μM). It accumulates ROS and inhibits the NF-κB/MAPK signaling pathway to exert anti-inflammatory effects, showing beneficial effects on cartilage destruction and inflammatory cell infiltration in a rat model of arthritis.

Etretinate (Ro 10-9359) is an oral aromatic retinoid acid which is effective in psoriasis and other dermatological syndromes. It activates retinoid receptors, causing an induction of cell differentiation, inhibition of cell proliferation, and inhibition of tissue infiltration by inflammatory cells.