chemokines

3-Hydroxykynurenamine, also known as 3-Hydroxy-L-kynurenamine or 3-HKA, is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1 NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction.This compound is unstable in powder form and other related salt forms are recommended.

Valencene (NSC-148969) is a sesquiterpenoid isolated from Cyperus rotundus and is an aroma component of citrus fruits and citrus-derived odors.ValenceneValencene has anti-allergic, anti-inflammatory, anti-melanogenic, and antioxidant activities. Valencene inhibits the overexpression of Th2 chemokines and pro-inflammatory chemokines by blocking the NF-κB pathway.

KS370G (Caffeic Acid Phenethyl Amide) inhibits UUO-induced renal fibrosis marker expression. KS370G is an orally active hypoglycemic and cardioprotective agent that reduces collagen deposition in obstructed kidneys and significantly decreases renal expression of inflammatory chemokines adhesion molecules and monocyte markers and improves left ventricular hypertrophy and function in the heart of pressure-overloaded mice.KS370G can be used to study renal obstructive nephropathy.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8 9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26 DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630 624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20 2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

CCR2 antagonist 4 (Teijin compound 1) is a potent and specific CCR2 antagonist with IC50 values of 180 nM and 24 nM for CCR2 inhibition and MCP-1-induced chemotaxis inhibition, respectively.

TMC353121 is a respiratory syncytial virus (RSV) fusion inhibitor with anti-RSV activity that inhibits the production of the inflammatory cytokines TNF-α, IL-6, and IL-1β, as well as chemokines, KC, IP-10, MCP, and MIP1-α.

Met-RANTES (human) acetate is the acetate salt form of Met-RANTES (human). It acts as an antagonist for CCR1 and CCR5 receptors. This compound inhibits the human chemokines MIP-1α and MIP-1β, with respective IC50 values of 5 and 2 nM. Additionally, Met-RANTES (human) acetate reduces bone destruction and alleviates adjuvant-induced arthritis (AIA) in rats.

SHP2-IN-35 (Compound 3f) functions as an inhibitor of SHP2. It exhibits antiproliferative activity in cancer cell lines RKO, SW480, and CT26, with IC50 values of 5.72 μM, 3.71 μM, and 1.42 μM, respectively. SHP2-IN-35 inhibits the PI3K-Akt signaling pathway, regulates the expression of cell cycle-related genes, and induces mitochondrial autophagy (autophagy). Within the tumor microenvironment (TME), SHP2-IN-35 suppresses the expression of certain cytokines and chemokines, thereby modulating tumor progression.

AMG 487 is an effective and selective antagonist of chemokine receptor 3. AMG 487 inhibited CXCR3-mediated cell migration induced by three CXCR3 chemokines, IP-10, ITAC and MIG (IC50: 8, 15 and 36 nM, respectively).

Noricaritin, a flavonoid derived from Epimedium root, induces cell proliferation in lung tissue and inhibits the production of pro-inflammatory cytokines and chemokines in human lung epithelial cells.

K 76 Carboxylic acid effectively blocks human complement from forming tumor cell chemokines.

Antileukinate is a synthetic hexapeptide with an acetylated amino terminus and an amidated carboxyl terminus that inhibits the binding of CXC chemokines to the chemokine receptor CXCR2. It inhibits IL-8 binding to neutrophils (Ki = 2.7-13 μM), prevents neutrophil chemotaxis and β-glucuronidase release, and blocks IL-8-induced skin edema in rabbits. At 53 mg/kg, antileukinate has been shown to protect mice against acute pancreatitis and associated lung injury.

IDR-1 is an antimicrobial peptide active against both Gram-positive and Gram-negative bacteria. This compound modulates innate immunity to counter infections while avoiding evident toxicities. Additionally, IDR-1 exhibits anti-inflammatory and anti-infective properties, increases the levels of monocyte chemokines, and reduces the release of pro-inflammatory cytokines.

IMMH001, also known as SYL930, is an orally active compound that exhibits potent selectivity as an agonist for the S1P1 receptor, which is the sphingosine-1-phosphate receptor 1. This compound effectively reduces the levels of various chemokines and proinflammatory cytokines, such as IL-1β, IL-5, IL-18, IP10, CCL3, and CCL5. IMMH001 finds utility in research focused on rheumatoid arthritis (RA) [1] [2].

Sophocarpine, a major ingredient of Sophora alopecuroides, has a wide range of pharmacological effects.

GA-O-02, an 18β-Glycyrrhetinic acid (GA) derivative, functions as a powerful antimicrobial and anti-inflammatory agent. This compound inhibits NO, pro-inflammatory cytokines, and chemokines to exert its anti-inflammatory effects. Additionally, GA-O-02 demonstrates significant antimicrobial activity against Gram-positive bacteria.

GA-O-06, an 18β-Glycyrrhetinic acid derivative, serves as a potent antimicrobial and anti-inflammatory agent. It achieves its anti-inflammatory effects by inhibiting NO, pro-inflammatory cytokines, and chemokines, while demonstrating significant antimicrobial activity against Gram-positive bacteria.

PB118 has the capacity to effectively clear Aβ deposits by augmenting phagocytosis, enhance the tubulin/microtubule network through increased acetyl α-tubulin levels, modulate various inflammation-associated cytokines and chemokines, and notably diminish phospho-tau (p-tau) levels linked to Alzheimer's disease (AD). The IC50 of PB118 for HDAC6 is 5.6 nM.

DPP-4-IN-8 (compound 27) is a potent and selective inhibitor of dipeptidyl peptidase 4 (DPP4), with an inhibition constant (Ki) of 0.96 μM. It inhibits the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells and dose-dependently reduces the expression of chemokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [1].

Murabutide, a safe synthetic immunomodulator, diminishes the expression of CD4 and CCR5 receptors and promotes the secretion of high levels of beta-chemokines, thereby enhancing nonspecific resistance to viral infections. It does not impact virus entry, reverse transcriptase activity, or the formation of early proviral DNA in the cytoplasm of infected cells [1].

Zharp1-211 is a selective and potent RIPK3 inhibitor that significantly reduces the expression of JAK stat1-mediated chemokines and MHC class II molecules in IECs, restores intestinal homeostasis, and inhibits graft-versus-host disease (GVHD) for gastrointestinal inflammation.

BRD5075 is an effective activator of GPR65, stimulating the production of cAMP in a GPR65-dependent manner. Additionally, it reduces the gene expression of IL-1, IL-2, TNF, and chemokines. BRD5075 holds potential for researching multiple sclerosis and inflammatory bowel disease (IBD).

Myristicin (Myristicine) is a natural product found in spices and umbelliferous plants. Myristicin has anti-cholinergic, Antibacterial, and hepatoprotective effects, it also has anti-inflammatory properties related with its inhibition of NO, cytokines,chemokines, and growth factors in dsRNA-stimulated macrophages via the calcium pathway. Myristicin can induce Apoptosis as characterised by alterations in the mitochondrial membrane potential, cytochrome c release, Caspase-3 activation, PARP-cleavage and DNA fragmentation.

Lintuzumab (HuM-195) is a non-coupled humanized mouse monoclonal antibody directed against the cell-surface myelomonocyte differentiation antigen, CD33, with anti-leukemic activity that reduces the production of TNFα-induced pro-inflammatory cytokines and chemokines by AML cells.Lintuzumab has antitumor activity and induces cell death directly via CDC or ADCC. Lintuzumab has anti-tumor activity and induces cell death directly via CDC or ADCC.