marrow-derived macrophages

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

NDMC101 is an inhibitor of dipeptidyl peptidase-IV activity in human T cells and exhibits immunomodulatory effects. It also acts as a novel inhibitor of NFATc1 and NF-κB activity.

NLRP3-IN-49 (compound Z48) is a potent and specific inhibitor of NLRP3, displaying IC50 values of 0.26 μM in THP-1 cells and 0.21 μM in mouse bone marrow-derived macrophages. It directly binds to the NLRP3 protein with a dissociation constant (Kd) of 1.05 μM, effectively preventing the assembly and activation of the NLRP3 inflammasome, thereby exhibiting anti-inflammatory properties. NLRP3-IN-49 is utilized in the research of inflammatory bowel disease.

Cyclic di-IMP (sodium salt) (c-di-IMP) is a synthetic second messenger structurally related to the bacterial second messengers cyclic di-GMP and cyclic di-AMP . C-di-IMP has adjuvant properties when co-administered with antigens in vitro and by mucosal routes in vivo. C-di-IMP enriches the population of MHC class I and II, CD80, CD86, CD40, and CD54 positive dendritic cells derived from murine bone marrow. It also stimulates macrophages at 500 ng/ml. Mice immunized with β-galactosidase (β-gal) plus c-di-IMP through the intranasal route show a humoral immune response, evidenced by an increase in IgG titers up to 2-fold compared to mice immunized with β-gal alone. Mice immunized with β-gal plus c-di-IMP also exhibit a Th1/Th2 response, indicating that the adjuvant activity of c-di-IMP leads to a cellular immune response as well.

Potent and selective p38α and p38β degrader (DC50 < 50 nM). Displays no significant degradation of p38γ, p38δ, JNK1/2 or ERK1/2. Inhibits phosphorylation of MK2 in UV-treated cancer cells and LPS-stimulated bone marrow-derived macrophages (BMDM). Exhibits similar effect to p38α gene knockout in BBL358 cells. Active in vivo.

Potent and selective GPR84 biased agonist (EC50 = 33 nM). Exhibits no significant activity in a panel of 168 other GPCRs. Exhibits bias for G protein signaling pathways. Induces morphological changes in primary murine bone marrow-derived macrophages (BMDMs) in a cellular impedance assay, and promotes phagocytosis by M1 polarized U937 cells. Induces migration of primary human monocytes, but has no effect on macrophage chemotaxis.

YHS-12, a ionizable cationic lipid (pKa = 6.506), has been utilized both in vitro and in vivo for delivering siRNA and mRNA via lipid nanoparticles (LNPs). These LNPs comprise YHS-12 and a targeting peptide CRVLRSGSC aimed at macrophages, encapsulating chimeric antigen receptor mRNA targeted at methicillin-resistant Staphylococcus aureus (MRSA) and siRNA against caspase-11. The LNPs have enhanced the phagocytic efficiency against MRSA in RAW 264.7 macrophages and primary murine bone marrow-derived macrophages (BMDMs). Administered intravenously, these LNPs have reduced bacterial load in the bloodstream and increased survival rates in a sepsis model in cyclophosphamide-induced immunosuppressed mice.

Cheilanthifoline has anti-osteoclastogenic property, it gives significant inhibitions on receptor activator of nuclear factor-κB ligand-induced differentiation of mouse bone marrow-derived macrophages into multinucleated osteoclasts.

SPA0355 is a thiourea derivative with antioxidant and anti-inflammatory properties. It inhibits RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclastogenesis in primary bone marrow-derived macrophages and suppresses the activation of MAPKs, Akt, and NF-κB pathways. Furthermore, SPA0355 enhances osteoblast differentiation by increasing alkaline phosphatase activity and mineralized nodule formation. It protects ovariectomized mice from bone loss by stimulating osteoblast differentiation and inhibiting osteoclast resorption, making it a potential candidate for studying postmenopausal osteoporosis.

TLR7 agonist 29 (Compound 1) is an activator of TLR7, displaying an EC50 of 5.2 nM for human TLR7 and 48.2 nM for mouse TLR7. It can activate bone marrow-derived macrophages (BMDM) and stimulate myeloid cells within the tumor microenvironment, enhancing the expression of PD-L1, CD86, and IFN-α. Additionally, TLR7 agonist 29 can serve as a payload for synthesizing ADCs.

NFAT inhibitor. Inhibits LPS or LPS plus IFN-γ-induced IL-12 p40, IL-12 p70, IL-23 and TNF secretion from bone marrow-derived macrophages (BMDMs). Also attenuates NO production and Nos2 mRNA expression in LPS-stimulated BMDMs. Improves symptoms in a mouse

LL-37 is a cationic and α-helical antimicrobial peptide expressed in human bone marrow, testis, granulocytes, and gingival epithelium and is upregulated in psoriatic lesions. It inhibits growth of Gram-positive E. coli D21 and Gram-negative B. megatarium in a concentration-dependent manner and LL-37 expression is induced in A549 epithelial cells, alveolar macrophages, neutrophils, and monocyte-derived macrophages following M. tuberculosis infection. LL-37 binds sheep erythrocytes coated with S. minnesota Re-LPS and induces agglutination with a minimal agglutinating concentration (MAC) of 12.1 μg/ml. It is a chemoattractant for, and can induce calcium mobilization in, human monocytes, neutrophils, and T cells that naturally express formyl peptide receptor-like 1 (FPRL1) and FPRL1-transfected HEK293 cells. LL-37 (10-15 μM) pretreatment of dengue virus type 2 (DENV-2) reduces its infectivity as well as levels of viral genomic RNA and NS1 antigen. In vivo, LL-37 inhibits cecal ligation and puncture-induced caspase-1 activation and pyroptosis of peritoneal macrophages, reduces levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α, and improves survival in polybacterial septic mice.

Resolvin conjugate in tissue regeneration 1 (RCTR1) is a specialized pro-resolving mediator (SPM) biosynthesized from docosahexaenoic acid by isolated human macrophages and apoptotic polymorphonuclear (PMN) neutrophils.1It has been found in human spleen and bone marrow.2RCTR1 is produced via lipoxygenase-mediated oxidation of DHA to 7(S)-8-epoxy-17(S)-HDHA, which is conjugated to glutathione.1,2,3RCTR1 (10 nM) increases phagocytosis ofE. colior apoptotic neutrophils in isolated human monocyte-derived macrophages.2It decreases chemotaxis induced by leukotriene B4in isolated human neutrophils when used at a concentration of 10 nM. RCTR1 (1 and 10 nM) accelerates tissue regeneration in planaria. Intraperitoneal administration of RCTR1 (100 ng/animal) shortens the inflammatory resolution period and decreases inflammatory exudate neutrophil infiltration in a mouse model ofE. coli-induced peritonitis. 1.Dalli, J., Ramon, S., Norris, P.C., et al.Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathwaysFASEB J.29(5)2120-2136(2015) 2.de la Rosa, X., Norris, P.C., Chiang, N., et al.Identification and complete stereochemical assignments of the new resolvin conjugates in tissue regeneration in human tissues that stimulate proresolving phagocyte functions and tissue regenerationAm. J. Pathol.188(4)950-966(2018) 3.Rodriguez, A.R., and Spur, B.W.First total synthesis of pro-resolving and tissue-regenerative resolvin sulfido-conjugatesTetrahedron Lett.58(16)1662-1668(2017)

HSP90-IN-31 (compound Be01) reduces the expression of CD80 and CD86 on dendritic cells (DC). It also diminishes the production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in bone marrow-derived dendritic cells (BMDC) and peritoneal macrophages stimulated by LPS. Additionally, in a delayed-type hypersensitivity (DTH) mouse model, HSP90-IN-31 alleviates ear swelling and decreases pro-inflammatory cytokines in the spleen.

3'4'7-Trihydroxyflavone can markedly inhibit the receptor activator of nuclear factor kappa B ligand (RANKL) induced osteoclastic differentiation from mouse bone marrow derived macrophages (BMMs), it inhibits osteoclastogenesis via nuclear factor of activ