interleukin-2 (il-2)

1. Linalool (Linalol), a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. 2. Linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition. 3. Linalool biosynthesis and accumulation might be involved in plant defense against bacterial and fungal pathogens and be associated with field resistance to citrus canker. 4. Linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6.

Safrole oxide was found to significantly inhibit neuronal cell growth and induce apoptosis. Safrole oxide elevated the levels of cyclooxygenase 2 (COX-2), interleukin-8 (IL-8) and reactive oxygen species (ROS), which was accompanied by nuclear factor-kappa B (NF-κB) nuclear translocation during the transdifferentiation, suggesting safrole oxide may induce endothelial cell transdifferentiation into functional neuron-like cells.

Triamcinolone (Aristocort) is a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. Upon cell entry, triamcinolone binds to and activates the glucocorticoid receptor, which leads to translocation of the ligand-receptor complex to the nucleus and induces expression of glucocorticoid-responsive genes such as lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both mediators of inflammation. In addition, pro-inflammatory cytokine production, including interleukin (IL)-1and IL-6, and the activation of cytotoxic T-lymphocytes is also inhibited. T-cells are prevented from making IL-2 and proliferating. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis through increasing Ikappa-B expression and curtailing activation of nuclear factor (NF)kappa-B.

Ppc-1 is a chemical compound known for its inhibitory effects on the Gram-negative periodontopathogen Porphyromonas gingivalis. It acts as a mitochondrial uncoupler, enhancing mitochondrial oxygen consumption without affecting ATP production. Additionally, Ppc-1 serves as a cell-permeate inhibitor of interleukin-2 (IL-2). This compound exhibits various beneficial activities, including anti-obesity, antibacterial, and anti-inflammatory properties.

HPK1-IN-43 (compound 9f) is an HPK1 kinase inhibitor with an IC50 value of 0.32 nM. It inhibits the phosphorylation of the downstream protein SLP-76 in PBMC cells and enhances the secretion of interleukin 2 (IL-2) and interferon-γ (IFN-γ). HPK1-IN-43 is applicable to cancer research.

GLPG4970 is a potent, selective, orally active dual inhibitor of salt-inducible kinases 2 and 3 (SIK2/SIK3), with IC50 values of 0.3 nM and 0.7 nM, respectively. It exhibits weak inhibition of the hERG channel, with an IC50 value of 29 μM. GLPG4970 reduces the release of tumor necrosis factor α (TNFα) and increases the release of interleukin 10 (IL-10). This compound is applicable for research in inflammation and immunology, such as studies on colitis.

Diflorasone is a synthetic glucocorticoid with anti-inflammatory and immunosuppressive properties. Like other glucocorticoids, diflorasone enters the cell by diffusion across the cell membrane and binds to the glucocorticoid receptor (GR) in the cytoplasm

Ro26-4550 is a competitive reversible inhibitor of interleukin-2 (IL-2) binding to IL-2R α-subunit (IC50 = 3 μM).

Ginsenoside Rh1 (Sanchinoside B2) , one of the main constituents of Panax ginseng, exhibits anti-inflammatory effect.

Clerodendrin (Apigenin-7-O-glucuronopyranosyl(1-2)-glucuronopyranoside) is a new neodentate diterpenoid isolated from the leaves of Clerodendron trichotomm, a radish sawfly Athalia Clerodendrin is an interleukin-4 (IL-4) inhibitor and β-hexosaminidase (Hex) inhibitor.

NSC 247030 inhibits interleukin 2 (IL-2) production.

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

Resolvin D5 is an oxidised lipid mediator derived from docosahexaenoic acid (DHA) with anti-inflammatory properties. It inhibits the production of interleukin-6 (IL-6) and chemokine CCL5 in LPS-stimulated THP-1 cells via the ERK-NF-κB signalling pathway.

JC-171, a selective inhibitor of the NLRP3 inflammasome, effectively inhibits LPS/ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8.45 μM[1].

BMSpep-57, a potent macrocyclic peptide inhibitor, competitively disrupts the PD-1/PD-L1 interaction, demonstrating a significant inhibitory concentration (IC50) of 7.68 nM. It exhibits binding affinity towards PD-L1 with dissociation constants (Kd) of 19 nM and 19.88 nM in MicroScale Thermophoresis (MST) and Surface Plasmon Resonance (SPR) assays, respectively. This compound enhances T cell functionality by promoting Interleukin-2 (IL-2) production within Peripheral Blood Mononuclear Cells (PBMCs).

INCB16562 is a novel, selective, and orally bioavailable small-molecule inhibitor of JAK1 and JAK2 markedly selective over JAK3. Treatment of myeloma cells with INCB16562 potently inhibited interleukin-6 (IL-6)-induced phosphorylation of STAT3. INCB16562 abrogated the protective effects of recombinant cytokines or bone marrow stromal cells and sensitized myeloma cells to cell death by exposure to dexamethasone, melphalan, or bortezomib. Oral administration of INCB16562 antagonized the growth of myeloma xenografts in mice and enhanced the antitumor activity of relevant agents in combination studies. INCB16562 is a potent JAK1/2 inhibitor and that mitigation of JAK/STAT signaling by targeting JAK1 and JAK2 will be beneficial in the treatment of myeloma patients, particularly in combination with other agents. ( source: Neoplasia. 2010 Jan;12(1):28-38. ).

1. Monotropein (Monotropeine) has antinociceptive action. 2. Monotropein has anti-apoptosis and anti-catabolic activity in chondrocytes. 3. Monotropein has anti-inflammatory action by inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis. 4. Monotrope ininhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages.

1. Mulberroside has nephroprotective, hypoglycemic, and antidiabetic effects. 2. Mulberroside A is a glycosylated stilbene of oxyresveratrol; thus, the deglycosylation of Mulberroside A resulted in enhanced inhibition of melanogenesis. 3. Mulberroside A has anti-inflammatory antiapoptotic effects. by decreasing the expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 and inhibiting the activation of NALP3, caspase-1, and nuclear factor-κB and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38.

PCC0208018 is a novel activator of effector T cells, enhancing T cell proliferation and activation to release interferon gamma (IFN-γ) and interleukin-2 (IL-2) without blocking the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) binding and not directly affecting tumor cell viability in vitro.

Denileukin diftitox (DAB 389IL-2), a fusion protein toxin combining diphtheria toxin (DT) and interleukin 2 (IL-2), selectively depletes cells with the high-affinity IL-2 receptor (IL-2R), specifically CD25. By binding to these cells, it introduces diphtheria toxin to inhibit protein synthesis, leading to cell depletion [1] [2] [3].

Ac-YVAD-CHO (L-709049) acetate is a potent, reversible, and specific tetrapeptide interleukin-1β converting enzyme (ICE) inhibitor, also demonstrating specificity for caspase-1. It exhibits K_i values of 3.0 nM in mice and 0.76 nM in humans, underscoring its efficacy. Additionally, Ac-YVAD-CHO acetate inhibits the production of mature IL-1β, highlighting its therapeutic potential [1] [2] [3].

ITK Degrader 1, a highly selective interleukin-2-inducible T-cell kinase (ITK; DC50=3.6 nM in vivo in mice) degrader, induces rapid and prolonged degradation of ITK and effectively suppresses IL-2 secretion (EC50=35.2 nM, Jurkat cells) stimulated by anti-CD3 antibody in vivo. Additionally, it demonstrates favorable plasma exposure levels [1].

Myelopeptide-2, a peptide isolated from the supernatant of porcine bone marrow cell cultures, can restore the mitogenic reactivity of human T lymphocytes inhibited by HL-60 leukemia cells or measles virus conditions. It also enhances depressed interleukin-2 (IL-2) synthesis and interleukin-2 receptor (IL-2R) expression, playing a role in immunity homeostasis. This compound shows potential for application in antitumor and antivirus research [1] [2].

Clazakizumab is a humanized monoclonal antibody targeting human interleukin -6(IL-6) with high affinity. By directly binding IL-6 ligand, it blocks its interaction with IL-6 receptor (IL-6α) and signal co-receptor gp130, thus inhibiting the activation of downstream JAK/STAT signaling pathway and weakening the inflammatory response. Clazakizumab can be used in the study of psoriasis arthritis and antibody-mediated organ transplant rejection.