CD4 cells

Cyclic-di-GMP disodium (5GP-5GP disodium) is a STING agonist and a second messenger in bacteria. It is involved in a variety of processes in prokaryotes, including biofilm formation, motility, and cell cycle progression. Cyclic-di-GMP disodium (5GP-5GP disodium) exhibits antiproliferative activity against cancer cells, inducing increased CD4 receptor expression and cell cycle arrest, and is a novel therapeutic agent that can be developed to prevent or treat cancer.

Anisperimus (LF 15-0195) is an immunosuppressant that enhances activation-induced T-cell death by promoting caspase-8 and caspase-10 activation at the DISC level, and prevents CNS autoimmunity by promoting the development of Foxp3-expressing regulatory CD4 T cells.

ML-209 is an antagonist of retinoic acid receptor-related orphan receptor γt (RORγt; IC50= 1.1 μM in a reporter assay).1It inhibits RORγt-induced transcription in HEK293T cells expressing the human receptor (IC50= 300 nM). ML-209 inhibits RORγt-dependent differentiation of isolated na?ve cord blood human CD4+T cells into Th17 T helper cells.

Fostemsavir Tris (BMS-663068 Tris) is the prodrug of BMS-626529,is a oral, safe and effective inhibitor of HIV-1 attachment. It inhibits human immunodeficiency virus type 1 (HIV-1) infection by binding to gp120 and interfering with the attachment of virus to CD4+ T-cells.

BI8626 is a ubiquitin ligase HUWE1 inhibitor with protective effects against spontaneous desiccation syndrome in NOD/ShiLtj mice.BI8626 inhibits intracellular cholesterol and decreases the expression of phosphorylated ZAP-70, CD25, and other activation markers, and inhibits the proliferation of CD4 T-cells.

DSPE-PEG(2000)-mannose, a pegylated and mannosylated derivative of 1,2-DSPE, has been employed in both in vitro and in vivo studies for delivering peptides, oligodeoxynucleotides, and siRNA via liposomes and lipid nanoparticles (LNPs). Fluorescently labeled LNPs containing DSPE-PEG(2000)-mannose predominantly accumulate in the liver and spleen of mice, significantly more so than in the brain, lungs, heart, kidneys, and pancreas. In immunization studies, liposomes encapsulating Human Papillomavirus type 16 (HPV16) E7 peptides with CpG oligodeoxynucleotides as an adjuvant led to reduced tumor volume and decreased numbers of CD4+ or CD8+ T cells and angiogenesis within tumors in a mouse lung cancer model using TC-1 cells.

SLW131 (Compound 10) is a CCR7 antagonist with strong affinity, showing a Ki of 9.85 nM. It inhibits CCL19-induced Go protein activation with an IC50 of 29.4 μM and β-arrestin2 recruitment with an IC50 of 6.0 μM. SLW131 also suppresses CCL19-induced morphological changes in primary BMDC cells and CCR7-mediated migration of mouse CD4+ T cells.

STAT3-IN-40 (Compound 8b) is an anticancer agent. It initiates immune responses in CD4+ and CD8+ T lymphocytes by inhibiting the expression and phosphorylation of STAT3, and induces ferroptosis and apoptosis in tumor cells. STAT3-IN-40 is valuable for research into cancer chemoimmunotherapy drugs.

PD-L1/LpxC-IN-1 (Compound 12b) is an inhibitor of PD-L1 and LpxC, with IC50 values of 5.2 μM and 0.081 μM, respectively. This compound disrupts bacterial lipopolysaccharide biosynthesis, leading to bacterial cell lysis and death. It effectively inhibits Gram-negative bacteria, exhibiting a minimum inhibitory concentration (MIC) of 0.25-0.5 μg/mL against K. pneumoniae ATCC 13883, E. coli ATCC 8739, S. typhimurium ATCC 14028, and P. aeruginosa ATCC 9027. Additionally, PD-L1/LpxC-IN-1 modulates the immune response by downregulating the expression of inflammatory cytokines IL-2 and IFN-γ, and upregulating CD4+ and CD8+ cells, thus activating the immune system and mitigating excessive inflammatory responses. In a mouse model of K. pneumoniae ATCC 13883 infection, PD-L1/LpxC-IN-1 demonstrated antibacterial activity.

SARS-CoV-2-IN-115 (Compound 3e) is a potent inhibitor of SARS-CoV-2, showing strong antiviral activity in infected Calu-3 cells with an EC50 of 1.7 μM. It effectively inhibits human dihydroorotate dehydrogenase (HsDHODH) activity with an IC50 of 1.5 μM. Importantly, SARS-CoV-2-IN-115 maintains immune response without affecting the proliferation of CD4 T cells.

A2AR modulator-1 (Compound 45) is a selective negative allosteric modulator of the adenosine A2a receptor (A2aR), with an IC50 value of 9 nM. It reduces the affinity of endogenous adenosine for the receptor and inhibits the activation of the cAMP signaling pathway. A2AR modulator-1 effectively restores pCREB phosphorylation in CD4+ T cells, reverses immunosuppression in the tumor microenvironment, and shows potential in inhibiting tumor growth and metastasis in a triple-negative breast cancer model.

RORγt inverse agonist 35 (Compound 22) is an RORγt inverse agonist with an IC50 of 1.51 μM. It significantly inhibits Th17 differentiation and pro-inflammatory characteristics in human CD4+ T cells. This compound can be utilized for research on Th17-driven autoimmune diseases, such as psoriasis, multiple sclerosis, and inflammatory bowel disease (IBD).

CCL-34 is an activator of Toll-like receptor 4 (TLR4). It significantly induces the expression of CD83 on dendritic cells (DC) and the production of IL-12p70 in a dose-dependent manner, thereby promoting DC maturation. CCL-34 enhances the allostimulatory activity of DC on the proliferation of naive CD4+CD45+RA+ T cells and their secretion of IFN-γ. Furthermore, CCL-34 can enhance antigen presentation capability in mice inoculated with doxorubicin-treated colorectal cancer cells. CCL-34 is applicable for research in immune stimulation.

ODN 2216 sodium is a human-specific TLR9 (toll-like receptor 9) ligand or agonist. It induces significant production of IFN-α and IFN-β. The compound stimulates IFN-α through pDC (plasmacytoid dendritic cells) and produces IL-12(p40) via DC (dendritic cells). ODN 2216 triggers peripheral blood mononuclear cells (PBMC) to produce IFN-γ indirectly, mediated by IFN-α/β. Additionally, ODN 2216 sodium can activate NK cells and enhance IFN-γ production in TCR-triggered CD4+ T cells.

TJU103 is a CD4 inhibitor that impedes the functionality of CD4 during activation, thereby suppressing autoreactive CD4+ T cells. In a mouse model of experimental autoimmune encephalomyelitis (EAE), TJU103 reduces monocyte infiltration in brain and spinal tissues. It downregulates Th1 and Th2 cytokine levels against proteolipid protein epitope 139-151 (PLPe) and exhibits inhibitory effects both after EAE symptom onset and subsequent antigen stimulation. TJU103 is applicable in research on autoimmune diseases such as EAE and multiple sclerosis (MS).

D-α-Methyl DOPA is an inhibitor of DQ8 peptide binding to MHC class II molecules. By occupying a binding site in the DQ8 peptide groove, D-α-Methyl DOPA prevents the DQ8 peptide from associating with MHCII molecules. This action blocks presentation to CD4+ T cells, thereby slowing or hindering the onset or progression of type 1 diabetes or celiac disease.

XAN-5 is a mitochondrial DNA G-quadruplex (mtG4) ligand with a Kd value of 3.8 μM. It selectively binds to and stabilizes mtG4 structures, disrupting mitochondrial gene transcription and DNA replication. This compound induces mitochondrial dysfunction, leads to excessive production of reactive oxygen species (ROS), causes G0 phase arrest, and triggers caspase-dependent apoptosis. XAN-5 inhibits autophagy and induces immunogenic cell death. In mouse liver cancer models, XAN-5 inhibits tumor growth and enhances tumor-infiltrating CD4+ and CD8+ T cells. Additionally, XAN-5 targets two tumor resistance mechanisms and is applicable in hepatic cancer research.

VA06 is a derivative of QS-21 that maintains strong adjuvant activity while significantly reducing toxicity. It can self-assemble into flexible worm-like micelles with continuous elongated nanostructures, enhancing drug encapsulation. VA06 induces antigen-specific antibody production, boosts the secretion of TNF-α, IFN-γ, and IL-2 in CD4+ and CD8+ T cells, and enhances the expression of immune-related and antiviral-related genes in mature dendritic cells. Without the need for liposomal formulations, VA06 simplifies production and storage processes. It is applicable for research on varicella-zoster virus infections and Mycobacterium tuberculosis infections.

TLR8 agonist10 is a specific TLR8 agonist with an EC50 of 0.019 μM in humans. It activates TLR8-mediated signaling pathways and functions as a latency-reversing agent capable of reactivating latent HIV-1 reservoirs. Additionally, TLR8 agonist10 can stimulate innate cytotoxic natural killer cells to target HIV-infected CD4+ T cells. This compound is useful for research related to HIV-1 infection.

BNM-III-170 free base is a CD4 mimetic compound that acts as an anti-HIV-1 agent. It binds to the Phe43 cavity on HIV-1 gp120, inhibiting the virus's entry into target cells, making it useful for research related to HIV-1 infection.

PJ27 is a dual PD-1/PD-L1/JAK1 inhibitor, exhibiting an IC50 of 414 nM for PD-1/PD-L1 and 786 nM for JAK1, with a Ka of 294 nM for human PD-1/PD-L1 and 473 nM for murine PD-1/PD-L1. It facilitates the infiltration of CD3+CD8+ and CD3+CD4+ cells into the tumor microenvironment, enhancing immune activation. In an LLC lung cancer mouse model, PJ27 shows a dose-dependent inhibition of tumor growth and is applicable for studies related to lung cancer.

5J-4 is a potent a blocker of calcium release-activated calcium (CRAC) channel and store-operated calcium entry (SOCE). 5J-4 reduces the production of IL-17 and decreases the expression of RORα and RORγt.

ARN-6039, an orally available inverse agonist of RORγ, targets Autoimmune Neuroinflammatory Demyelinating Disease. Its efficacy was demonstrated in a RORγ-activated IL-17A Prom/LUCPorter assay in HEK 293 cells (360 nM) and in IL-17 release from CD4+T cell assays (220 nM).

Naringenin chalcone (Isosalipurpol) has antiallergic activity Naringenin chalcone suppresses asthmatic symptoms by inhibiting Th2 cytokine production from CD4 T cells. Naringenin chalcone is a potent tomato flavonoid that improves adipocyte metabolic functions and exerts insulin-sensitizing effects by activating an adiponectin-related pathway. Naringenin chalcone exhibits anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages, may be useful for ameliorating the inflammatory changes in obese adipose tissue.