cell-macrophage

NHWD-870 is an effective and selective inhibitor of BET family bromodomain only binding to BRD2, BRD3, BRD4 (IC50 = 2.7 nM), and BRDT. NHWD-870 exhibits potent anti-tumor efficacies and suppresses cancer cell-macrophage interaction through the increase of tumor apoptosis and inhibition of tumor proliferation.

Dexamethasone is a glucocorticoid receptor agonist and IL receptor modulator with anti-inflammatory, immunosuppressive, and apoptosis-inducing activities. It inhibits the production of inflammatory miRNA-155 exosomes in macrophages, significantly reduces inflammatory cytokine expression in neutrophils and monocytes, suppresses LPS-induced macrophage inflammation, and induces autophagy. It is commonly used to induce animal models of depression, muscle atrophy, and hypertension, and holds potential in COVID-19 research.

Amiprilose (SM 1213) has anti-inflammatory activity and inhibits the proliferation of a variety of hyperproliferative cell types.Amiprilose induces lymphokine-induced macrophage activation and may be used in studies of rheumatoid arthritis and psoriasis.

Bestatin (Ubenimex) competitively inhibits many aminopeptidases, including B, N and leucine aminopeptidases. Ubenimex is a microbial metabolite and dipeptide with potential immunomodulatory and antitumor activities. Aminopeptidases has been implicated in the process of cell adhesion and invasion of tumor cells. Therefore, inhibiting aminopeptidases may partially attribute to the antitumor effect of ubenimex. This agent also activates T lymphocyte, macrophage, and bone marrow stem cell as well as stimulates the release of interleukin-1 and -2, thus further enhances its antitumor activity.

Dextran sulfate sodium salt (MW 4500-5500) is a polymer of dehydrated glucose and an inhibitor of complement and coagulation pathways. Dextran sulfate sodium salt (MW 4500-5500) can be used as an anticoagulant, antiviral agent and antilipidemic agent. Dextran sulfate sodium salt (MW 4500-5500) can prevent the HIV-1 virus from adsorbing onto host cells. Dextran sulfate sodium salt (MW 4500-5500) can inhibit NK cell-mediated cytotoxicity. Dextran sulfate sodium salt (MW 4500-5500) can inhibit the immediate blood-mediated inflammatory response (IBMIR).

Inosine pranobex (Delimmun) has a number of immunomodulatory effects, including inducing T-lymphocyte differentiation, augmenting macrophage and NK cell functions, and stimulating IL-2 production. Through these effects and others, isoprinosine shows antiviral activity and has applications against subacute sclerosing panencephalitis. It also restores depressed immune responses in Y patients after irradiation and reduces the incidence of infection in leukemia patients undergoing chemotherapy. It is most commonly used to treat the rare measles complication subacute sclerosing panencephalitis in conjunction with intrathecal interferon therapy.

KGP94 is an inhibitor of cysteine protease Cathepsin L(CTSL).

G150 inhibited interferon expression triggered by DSDNA with IC50 of 10.2 nM.G150 is an effective and highly selective inhibitor of human cyclic GMP-AMP synthase (H-CGAS).

Golotimod (SCV 07) is an antimicrobial dipeptide with immunomodulatory activity that significantly improves the efficacy of anti-tuberculosis therapy, induces thymic and splenic cell proliferation, modulates macrophage function, and inhibits STAT3 signaling.Golotimod has been used in the study of recurrent genital Herpes Simplex Virus 2 (HSV-2) infection and oral mucositis.

SJ-C1044 is an orally effective pan-RAF inhibitor demonstrating immunomodulatory and antitumor activities. It targets wild-type BRAF, wild-type CRAF, and BRAF(V600E) with IC50 values of 331, 257, and 187 nM, respectively. SJ-C1044 suppresses tumor cell proliferation by inhibiting kras activation and MEK-ERK phosphorylation. Additionally, it shows inhibition of VEGFR2, TIE2, and CSF1R, with IC50 values of 100, 23, and 235 nM respectively. The compound enhances the tumor immune microenvironment through inhibition of angiogenesis and modulation of macrophage function. SJ-C1044 is applicable for research in colorectal cancer.

PLD-IN-1 (Compound 3r) is an orally effective inhibitor of phospholipase D (phospholipaseD) with an IC50 of 1.97 μM. It reduces the expression of CD24, CD47, and PD-L1 while enhancing the expression of calreticulin, thereby modulating the immune evasion mechanisms of lung cancer cells by promoting the phagocytosis of cancer cells by macrophages. PLD-IN-1 inhibits the viability of lung cancer cell lines A549, HCC44, H460, and HCC15 with IC50 values of 18.44, 22.31, 24.85, and 21.45 μM, respectively. It induces apoptosis (apoptosis) in A549 cells and inhibits cell migration. Additionally, PLD-IN-1 increases pro-inflammatory M1 macrophage levels and decreases anti-inflammatory M2 macrophage levels, exhibiting anti-tumor activity in mouse models.

Lipid 16 is an ionizable lipid that facilitates the synthesis of lipid nanoparticles (LNP) for the delivery of mRNA and other payloads. It specifically targets the CD11bhi macrophage population as a potent cell-type specific ionizable lipid, eliminating the need for additional targeting components.

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.

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.

AN0128 (CRM-0005) is an anti-inflammatory boron-containing antibacterial agent that inhibits S. aureus, S. epidermidis, P. acnes, B. subtilis, and suppresses pro-inflammatory cytokine production in macrophage cell lines by inhibiting the p38 MAP kinase signaling pathway. It can be used in dermatological research.

Cimifugin (Cimitin) inhibits NO production induced by lipopolysaccharide in macrophage cell line RAW 264.7 and for 1, 1-diphenyl-2-picrylhydrazyl free-radical scavenging activity in cell-free bioassay system.

D-Trimannuronic acid is an alginate oligomer that originates from seaweed. It can induce TNF-α secretion by mouse macrophage cell lines, making it valuable in pain and vascular dementia research [1][2][3].

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.

Thiocarlide (isoxyl) is a thiourea derivative that was used in the 1960s to successfully treat tuberculosis (TB). It has considerable antimycobacterial activity in vitro and is effective against multi-drug resistant strains of Mycobacterium tuberculosis in the range of 1-10 µg/ml. [1] [2] At concentrations of 10 µM, isoxyl inhibits the synthesis of M. bovis during six hours of exposure which is similar to isoniazid (INH) and ethionamide (ETH), two other predominant anti-tuberculosis drugs. Unlike INH and ETH, isoxyl also partially inhibits the synthesis of fatty acids. Isoxyl shows no acute toxicity against primary macrophage cell cultures as demonstrated by diminution of redox activity.[2]

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)

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].

Roquinimex (FCF89) (Linomide) is a quinoline derivative immunostimulant which increases NK cell activity and macrophage cytotoxicity; inhibits angiogenesis and reduces the secretion of TNF alpha.

CCR4 antagonist 3-1 is a less active chemokine receptor 4 (CCR4) antagonist that inhibits [125I]TARC (thymus and activation-regulated chemokine) with an IC50 value of 1.7 μM. CCR4 antagonist 3-1 inhibits the binding of radiolabeled [125I]TARC and macrophage-derived chemokine ( MDC) to CEM cell surface and inhibits TARC-mediated CEM cell migration in vitro with an IC50 value of 6.4 μM. CCR4 antagonist 3 inhibited the binding of radiolabeled [125I]TARC and macrophage-derived chemokine (MDC) to the CCR4 receptor on the surface of CEM cells and inhibited TARC-mediated migration of CEM cells in vitro with an IC50 value of 6.4 μM.

MIF098, a macrophage migration inhibitory factor (MIF) antagonist, inhibits pulmonary hypertension associated with SLE and the proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). MIF098 may also be used to study idiopathic pulmonary hypertension.