macrophages

ADH-503 (GB1275) is a potent agonist of the integrin CD11b to mitigate myeloid cell immunosuppression.

Dexamethasone (Hexadecadrol) is a glucocorticoid receptor agonist and an IL receptor modulator. Dexamethasone has anti-inflammatory and immunosuppressive activity and induces autophagy. Dexamethasone inhibits LPS-induced inflammatory responses in macrophages.

Terbutaline is a short-acting agonist of β2-adrenergic receptor (β2-AR) . It is an active metabolite of bambuterol

3,7,4'-Trihydroxyflavone(5-Deoxykampferol) is a DNA-breaking flavonoid isolated from rosewood heartwood. It inhibits osteoclast differentiation, actin ring formation, and bone resorption in RAW 264.7 cells and bone marrow macrophages induced by NF-κB ligand (RANKL) receptor activators.

Bisdemethoxycurcumin (Curcumin III) is a natural demethoxy derivative of curcumin. It is a potent activator of macrophage phagocytosis, interacting with 1α, 25-dihydroxy vitamin D3 to stimulate amyloid-β clearance by macrophages (optimal stimulation at 100 nM BDMC) [1]. More stable than curcumin in physiological media, BDMC suppresses proliferation of cancer cells [2]. It down-regulates the transcriptional coactivator p300, suppressing the Wnt/β-catenin pathway, and inhibits LPS induction of iNOS expression [3].

LCB 03-0110 Dihydrochloride is a potent inhibitor of the c-Src kinase (IC50 = 1.3 nM) and tyrosine kinases in the BTK and SYK family, as well as in the DDR2 family. It inhibits LPS-induced activation of macrophages and TGF-β1-induced activation of fibroblasts in vitro, inhibits activation of macrophages and fibroblasts, and inhibits scarring in wound healing models.

Rabeximod is a potent immunomodulator that reduces the severity of autoimmune diseases in rat models. Rabeximod inhibits arthritis in a time-dependent manner by stimulating TLR2 and TLR4 downstream to block the activation of inflammatory cells, most likely macrophages. Rabeximod effectively reduces brain antigen presentation in mice during anti-inflammatory therapy for traumatic brain injury.

RS09 2TFA (1449566-36-2 free base) is a TLR4 agonist. Promotes NF-κB nuclear translocation and induces inflammatory cytokine secretion in RAW264.7 macrophages in vitro. It acts as an adjuvant in vivo and enhances X-15 specific antibody serum concentrations.

Hulupinic acid is the main oxidation product of hop acid, which may inhibit the production of NO in macrophages RAW 264.7 cells.

Traxanox TFA is an orally available diuretic. Traxanox TFA enhances phagocytosis of yeast granules by mouse peritoneal macrophages or rat peritoneal polymorphonuclear leukocytes in vitro. Traxanox TFA restores inhibition of antibody production in BALB/c mice. Traxanox TFA is also effective in restoring antibody production in BALB/c mice. Traxanox TFA has been shown to enhance phagocytosis in BALB/c mice.

PU-WS13 hydrobromide is a GRP94 inhibitor with anti-inflammatory activity and inhibits the proliferation of M2-like macrophages in mouse TNBC tumors.

2-(Chloromethyl)-4-(4-nitrophenyl)thiazole is a natural product derived from Astragalus propinquus.2-(Chloromethyl)-4-(4-nitrophenyl)thiazole exhibits anticancer activity. 2-(Chloromethyl)-4-(4-nitrophenyl)thiazole possesses anticancer activity and has been shown to be active in hepatocellular carcinoma (HCC) by inhibiting the M2 polarization of tumor-associated macrophages (TAM).

4-methoxylonchocarpin was isolated from the roots of Abrus precatorius as a potent anti-inflammatory compound. 4-methoxylonchocarpin inhibited NF-κB-activated TNF expression by inhibiting the binding of LPS to TLR4 in macrophages and suppressed TNBS-induced colitis in mice.

Adenosine N1-oxide (1-Oxoadenosine), which is found in royal jelly, inhibited the secretion of inflammatory mediators by activated macrophages and reduced lethality in lipopolysaccharide (LPS)-induced endotoxin shock.

CALP2 acetate is an antagonist of calmodulin showing high affinity for binding to the CaM EF-hand/Ca2+-binding site with a Kd of 7.9 µM. CALP2 acetate potently inhibits of adhesion and degranulation. CALP2 acetate is also a strong activator of alveolar macrophages. CALP2 acetate inhibits CaM-dependent phosphodiesterase activity and increases intracellular Ca2+ concentrations.

Antitumor agent-19 is a modulator of tumor-associated macrophages with EC50s of 17.18 μM and 18.87 μM in the RAW 264.7 cells and the BMDM cells.

The impact of spleen tyrosine kinase (Syk) signaling might be prominent in lupus because (i) Syk is a shared downstream signaling molecule among circulating immune complex, LPS, and (1→3)-β-D-glucan (BG), and (ii) all of these factors are detectable in the serum of Fc gamma receptor IIb-deficient (FcgRIIb-/-) mice with sepsis. Syk inhibition downregulated several inflammatory pathways in FcgRIIb-/- macrophages activated with BG + LPS suggesting the potential anti-inflammatory impact of Syk inhibitors in lupus. Indeed, administration of a Syk inhibitor prior to cecal ligation and puncture (CLP) sepsis in FcgRIIb-/- mice reduced baseline lupus-induced proinflammatory cytokines and attenuated sepsis severity as evaluated by mortality, organ injury, serum LPS, and post-sepsis serum cytokines.

C-Reactive Protein (CRP) 77-82 acetate is the 77-82 fragment of C-Reactive Protein. C-Reactive Protein (CRP), the prototypic marker of inflammation, is a cardiovascular risk marker and may promote atherogenesis.C-reactive protein (CRP) is an annular (ring

C-Reactive Protein (CRP) 174-185 acetate is an acute phase serum protein synthesized in response to inflammatory cytokines, produces antitumor effects in animals. The fragment CRP (174-185) (RS-83277) shows similar activity by significantly enhancing the

Imupedone (LF 1695) is a synthetic immunomodulator that modulates T lymphocytes and macrophages, induces T-cell differentiation of bone marrow precursor cells, and increases the proliferative response of lymphocytes to mitogens, antigens, and allogeneic cells.CAS 번호13483-84-5

Talviraline (Bay 10-8979) is an RNA-induced DNA polymerase inhibitor.Talviraline is a potent inhibitor of HIV-1-induced cell killing and HIV-1 replication in a variety of human cell lines, as well as in fresh human peripheral blood lymphocytes and macrophages.

Maresin 1 is a small molecule compound biosynthesized by macrophages (MΦ) with significant anti-inflammatory activity that attenuates LPS-induced lung injury in mice by inhibiting neutrophil adhesion and decreasing the levels of pro-inflammatory cytokines, and stimulates intracellular Ca2+ production and secretion.

AKB-6899 is an inhibitor of prolyl hydroxylase domain 3 (PHD3) and increases the soluble form of the VEGF receptor (sVEGFR-1) production from GM-CSF-treated macrophages. AKB-6899 leads to stabilization of HIF-2α which induces sVEGFR-1 production from tumor-associated macrophages and decreases tumor growth.

Itaconate-alkyne (ITalk) is a bioorthogonal probe for quantitative and site-specific chemoproteomic profiling of itaconate in inflammatory macrophages and enables biochemical evaluation and proteomic analysis of its direct targets.

NLRP3-IN-NBC6 is a potent, selective NLRP3 inflammasome inhibitor with IC50 of 574 nM. NLRP3-IN-NBC6 acts independently of Ca 2+. NLRP3-IN-NBC6 inhibits Nigericin -induced inflammasome activation in THP-1 cells and Imiquimod -induced IL-1β release from LPS-primed bone marrow-derived macrophages (BMDMs) [1].

GSK2556286 (GSK286) is an orally active inhibitor of Mycobacterium tuberculosis (M. tuberculosis).GSK2556286 inhibits the growth of human macrophages with an IC50 value of 0.07 μM.GSK2556286 is effective against both multidrug-resistant (MDR) or extensively drug-resistant (XDR) and drug-sensitive (DS) M. tuberculosis. GSK2556286 is effective against multi-drug resistant (MDR) or extensively drug resistant (XDR) and drug sensitive (DS) Mycobacterium tuberculosis.

AzddMeC (Az-Dcme) is a nucleoside analog with antiviral activity and is an orally active and selective inhibitor of HIV-1 reverse transcriptase and HIV-1 replication.AzddMeC has an EC50 value of 9 nM against HIV-1-infected human PBM cells and 6 nM against HIV-1-infected human macrophages.

CJ-13,610 is an orally active and nonredox-type inhibitor of 5-lipoxygenase (5-LOX). CJ-13,610 inhibits the biosynthesis of leukotriene B4 and regulates the expression of IL-6 mRNA in macrophages.

BTB09089 (GPR65 agonist ) is a T cell death-associated gene 8 (TDAG8/GPR65)-specific agonist.BTB09089 induces TDAG8 expression and regulates cytokine production in T cells and macrophages.

NSC-37445 has anti-tumor activity, such as inhibits growth of bladder tumor cells in a nude mice model , prevents the recurrence and progression of non-muscle-invasive urothelial cell carcinoma. NSC-37445 can significantly reduce the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and cause cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. 3. Flavokawain A (Flavokavain A) may exert anti-inflammatory responses by suppressing LPS-induced expression of pro-inflammatory mediators via blockage of NF-κB-AP-1-JNK/p38 MAPK signaling pathways in the murine macrophages.

Resiquimod (R848) is an imidazoquinoline amine and Toll-like receptor (TLR) agonist with potential immune response modifying activity. Resiquimod exerts its effect through the TLR signaling pathway by binding to and activating TLR7 and 8 mainly on dendritic cells, macrophages, and B-lymphocytes. This induces the nuclear translocation of the transcription activator NF-kB as well as activation of other transcription factors. This may lead to an increase in mRNA levels and subsequent production of cytokines, especially interferon-alpha (INF-a) and other cytokines, thereby enhancing T-helper 1 (Th1) immune responses. In addition, topical application of resiquimod appears to activate Langerhans' cells, leading to an enhanced activation of T-lymphocytes.

1. β-Anhydroicaritin exhibits immunosuppressive effect on the mouse macrophages stimulated by LPS. 2. β-Anhydroicaritin phytosomes can inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus. 3. β-Anhydroicaritin possesses significant protective effects on the zymosan-induced peritonitis mice, which might be associated with the regulation of Ca(2+); influx in macrophages and iNOS expression.

ISO-1 (MIF Antagonist) is an inhibitor of the dopachrome tautomerase activity, blocks the activation of NF-κB and TNF-α secretion from LPS-treated macrophages.

Bardoxolone (CDDO) is a synthetic oleanane triterpenoid that blocks the cellular synthesis of inducible nitric oxide synthase and inducible COX-2 in INF-γ-activated mouse macrophages with an IC50 value of 0.4 nM. By suppressing reactive oxygen and nitrogen species (ROS/RNS) formation, it promotes the cellular control of ROS/RNS levels that would lead to DNA damage associated with tumorigenesis. In various Y cell lines, Bardoxolone has been shown to specifically inhibit proliferation and induce apoptosis. Mechanism studies revealed that Bardoxolone is a ligand for peroxisome proliferator-activated receptor γ, and also that it induces genes regulated by Nrf2, including heme oxygenase-1 and eotaxin-1, which play a role in antioxidant response element signaling activity.

Polygalacin D shows anti- proliferation, anti-inflammary, and hepatoprotective activities, it can inhibit the expression of lipopolysaccharide (LPS)-induced iNOS and COX-2 protein and mRNA without an appreciable cytotoxic effect on RAW 264.7 macrophages, and can suppress induction by LPS of pro-inflammatory cytokines such as prostaglandin E2 (PGE2).

Platycodin D may stimulate TNF-α synthesis or inhibit degradation of TNF-α mRNA. Platycodin D (10/30 μM) suppresses prostaglandin E2 production in rat peritoneal macrophages stimulated by the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate (TPA). Platycodin D and D3 are useful as expectorant agents in the treatment of various airway diseases, they can increase mucin release from rat and hamster tracheal surface epithelial cell culture and also from intact rat trachea upon nebulization.

C29 is a novel inhibitor of TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages.

Sitravatinib (MGCD516) is an inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Met, c-Kit, PDGFRα/β, PDGFR, and Axl.

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.

TRPV2-selective blocker 1 (compound IV2-1) is a selective inhibitor of the TRPV2 channel, exhibiting an IC50 value of 6.3 μM. It specifically targets the TRPV2 channel without impacting related TRPV1, TRPV3, or TRPV4 channels. Additionally, this compound effectively suppresses TRPV2-mediated calcium influx in macrophages and inhibits their phagocytic activity [1].

Phaeocaulisin E (Compound 5), a guaiane-type sesquiterpene, inhibits LPS-induced NO production in RAW 264.7 macrophages, exhibiting an IC50 value of 10.3 µM [1].

Tuftsin diacetate, a tetrapeptide, is a macrophage/microglial activator. Tuftsin is a tetrapeptide, Thr-Lys-Pro-Arg, which resides in the Fc-domain of the heavy chain of immunoglobulin G. Tuftsin possesses a broad spectrum of activities related primarily

Sanggenone H may have antiphlogistic activity, it attenuated the secretion of TNF-α± and IL-1α² and inhibited the NF-κB nuclear translocation in LPS-stimulated macrophages.

Dioleoylphosphatidylglycerol (DOPG), a naturally occurring phospholipid, is synthesized through the action of aquaporin 3 (AQP3) and phospholipase D2 (PLD2). It functions to suppress the production of inflammatory mediators by macrophages triggered by the activation of toll-like receptor 2 (TLR2) by heat shock protein B4 (HSPB4) [1].

RS 09 TFA, a TLR4 agonist, promotes NF-κB nuclear translocation and induces the secretion of inflammatory cytokines in RAW264.7 macrophages in vitro. Additionally, as an adjuvant in vivo, RS 09 TFA enhances serum concentrations of X-15 specific antibodies when co-administered with X-15-KLH in mice.

Flunixin meglumine (Banamine) is an effective inhibitor of the enzyme cyclooxygenase with anti-inflammatory and antipyretic activity.

2,3-Dehydro-3,4-dihydro ivermectin, an ivermectin analog and anthelmintic, demonstrates efficacy against L. amazonensis promastigotes and amastigotes, with IC50 values of 13.8 and 3.6 µM, respectively, while maintaining a low cytotoxicity profile in macrophages (IC50 = 65.5 µM).

Protein conjugates in tissue regeneration 3 (PCTR3) is a specialized pro-resolving mediator (SPM) synthesized from docosahexaenoic acid . DHA is oxidized to 16S,17S-epoxy-protectin, which is converted to PCTR1 by glutathione S-transferase and to PCTR2 and PCTR3 via peptidases. PCTR3 is found in infected mouse spleens and resolving exudate as well as isolated human spleen and septic plasma. It is also found in both M1 and M2 macrophages differentiated from isolated human monocytes.

Beauveriolide I is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.78 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide I also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 6 μM).2 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Beauveriolide III is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.41 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide III also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 5.5 μM).2Beauveriolide III (25 and 50 mg/kg) reduces the size of aortic atherosclerotic lesions inLdlr-/-andApoE-/-mouse models of atherosclerosis. 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)