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.

Natalizumab is a recombinant humanized monoclonal antibody and a humanized monoclonal antibody inhibitor that selectively targets α4 integrin (CD49d). Natalizumab binds to the α4β1 heterodimer and blocks its interaction with vascular cell adhesion molecule 1. Natalizumab also prevents lymphocytes from entering the central nervous system, thereby preventing acute demyelinating relapses, and is used in the study of relapsing-remitting multiple sclerosis and Crohn’s disease. Natalizumab possesses anti-inflammatory and immunomodulatory activity, inhibiting the adhesion, retention, and transendothelial migration of immune cells, and reducing the infiltration of inflammatory cells into the central nervous system or affected sites. Natalizumab is also being studied for autoimmune or inflammation-related diseases such as B-cell lymphoma and non-infectious uveitis.

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.

LMP-420 is a selective inhibitor of tumor necrosis factor-α (TNF-α). It reduces the release of pro-inflammatory cytokines, such as IL-1β and IL-2, while inducing the expression of anti-inflammatory cytokine IL-10, and anti-apoptotic molecules SOCS-1 and Mn-SOD. LMP-420 also downregulates chemokines like IP-10 and MCP-1, which decreases immune cell infiltration. This compound shows potential for research into type 1 diabetes, inflammatory diseases such as colitis, and HIV-mycobacterium tuberculosis co-infection.

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.

CHNQD-01281 is a derivative of Brefeldin A and acts as an EGFR regulator. It exhibits potent antiproliferative activity against cancer cells, with IC50 values of 0.079 μM and 0.081 μM for T24 and J82 cells, respectively. CHNQD-01281 modulates both the EGFR/PI3K/AKT and EGFR/ERK pathways, influencing chemotactic effects on immune effector cells. It significantly inhibits tumor growth in T24 xenograft mouse models and extends survival in MB49 allograft mouse models by inducing cytotoxic T cell infiltration.

PARP1-IN-44 is a derivative of Olaparib and functions as an orally active PARP1 inhibitor with an IC50 of 0.6 nM. It also inhibits PARP2 (IC50 = 1.0 nM) and PARP7 (IC50 = 7.5 nM). PARP1-IN-44 demonstrates selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. It induces G2/M phase arrest, promotes apoptosis, increases reactive oxygen species (ROS) levels, and disrupts mitochondrial membrane potential. Additionally, PARP1-IN-44 inhibits PARylation and leads to the accumulation of γH2AX. It activates the cGAS-STING pathway, enhancing the expression of IFN-β and CXCL10. In a CT26 tumor mouse model, PARP1-IN-44 enhances CD8+ T cell infiltration, showcasing significant in vivo antitumor activity.

Copper ionophore I is an efficient carrier of copper ions that modulates intracellular copper levels to induce cuproptosis, with effects observed in cells such as 4T1 (IC50= 0.45 μM) and MDA-MB-231 (IC50= 1.21 μM). It elevates ROS, leading to mitochondrial dysfunction, and decreases the expression of proteins FDX1, DLAT, and LIAS. Additionally, it can activate immune-related pathways, enhancing T cell infiltration, making it a valuable compound for cancer research.

PTPN2/1-IN-4 (Compound WS35) is an orally active dual inhibitor of PTPN1 and PTPN2, with IC50 values of 12.8 nM and 5.8 nM, respectively. It modulates the IFNγ-JAK-STAT signaling pathway and significantly enhances CD8+ T cell tumor infiltration. PTPN2/1-IN-4 demonstrates potent anticancer activity, effectively inhibiting tumor growth in the B16-OVA syngeneic mouse model both as a monotherapy and in combination with anti-PD-1 antibody treatment.

TPST2-IN-1 is a potent and selective TPST2 inhibitor, with an IC50 of 946 nM and a Ka of 19.4 μM. It functions by inhibiting TPST2 activity, thereby increasing the phosphorylation level of Stat1 and upregulating the expression of the IFNγ-responsive gene CXCL10. Exhibiting antitumor activity, TPST2-IN-1 enhances T cell-mediated antitumor immunity, characterized by increased infiltration of effector CD8+ T cells. This compound is applicable in cancer research, such as studies involving colorectal cancer.