NOD-like Receptor (NLR) Agonist

Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide, consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. Muramyl dipeptide is an inducer of bone formation through induction of Runx2. Muramyl dipeptide directly enhances osteoblast differentiation by up-regulating Runx2 gene expression through MAPK pathways. Muramyl dipeptide is a NLRP1 agonist.

BMS-986299 (compound 112) is a first-in-class NLRP3 inflammasome agonist with an EC₅₀ of 1.28 μM. (patent WO2018152396A1).

Icariside I (GH01) is an orally active metabolite of icalin. Icariside I improves estrogen deficiency-induced osteoporosis by simultaneously regulating osteoblast and osteoclast differentiation. Icariside I promotes ATP (HY-B2176) or Nigericin (HY-127019)-induced mtROS production and NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Icariside I inhibits breast cancer proliferation, apoptosis, invasion, and metastasis by targeting the IL-6/STAT3 pathway. Icariside I is a kynurenine-AhR pathway inhibitor that alleviates cancer by blocking tumor immune escape.

NLRP3 agonist 1 (Compound 23) is an orally active NLRP3 agonist. NLRP3 agonist 1 can activate the enzyme Caspase-1 to cleave pro-IL-1β and pro-IL-18 proinflammatory cytokines into their mature forms.

C12-iE-DAP hydrochloride (Lauroyl-γ-D-glutamyl-meso-diaminopimelic acid hydrochloride) is a highly potent and selective NOD1 agonist, with an EC₅₀ of 0.027 nM in HEK-Blue cells expressing human NOD1. C12-iE-DAP hydrochloride activates the NOD1/RIPK2 signaling pathway and its downstream p38 MAPK and NF-κB, induces the expression of inflammatory mediators such as IL6 and IL8, and exerts synergistic effects with TLR4, Dectin-1 or Mincle signaling. C12-iE-DAP hydrochloride can be used in studies related to vascular inflammation, tumor metastasis and neuroinflammation.

2-Guanidinobezimidazole (2GBI) is a NLRP3 agonist with a K_D of 1.29 μM and a selective state-dependent HVCN1 blocker. 2-Guanidinobezimidazole directly binds NLRP3’s LRR domain, enhances NLRP3-ASC and NLRP3-NEK7 interactions, and drives NLRP3 inflammasome activation. 2-Guanidinobezimidazole can be used for the research of LLC lung carcinoma, B16F10 melanoma and ischemic stroke.

iE-DAP dihydrochloride is a Nod1 agonist. iE-DAP dihydrochloride activates NOD1, which in turn activates the NF-κB signaling pathway and MLCK signaling pathway, inducing cellular inflammatory responses and tight junction disruption. iE-DAP dihydrochloride downregulates the expression of ZO-1 and Occludin genes. iE-DAP dihydrochloride increases the secretion of IL-6, GRO-α, MCP-1, IL-8 and MIP-1β in term human trophoblast cell cultures. iE-DAP dihydrochloride triggers preterm birth in pregnant mice, reduces fetal body weight, and induces fetal inflammation. iE-DAP dihydrochloride can be used in studies related to mastitis and preterm birth.

M-TriDAP (N-Acetylmuramyl-L-Ala-γ-D-Glu-meso-diaminopimelic acid) is a NOD1/2 agoist and biological active peptide.

M-TriDAP (N-Acetylmuramyl-L-Ala-γ-D-Glu-meso-diaminopimelic acid) TFA is a NOD1/2 agoist and biological active peptide.

NOD1/TLR7 agonist-1 is a dual NOD1 and TLR7 agonist. NOD1/TLR7 agonist-1 exhibits adjuvant effects in mouse vaccine models and induces increased ovalbumin-specific IgG titers. NOD1/TLR7 agonist-1 can be used for research on immune-related diseases.

NOD2 agonist 2 (compound 23) enhanced the antigen presentation of mouse bone marrow-derived dendritic cells (BMDCs), highlighting its potential as a vaccine adjuvant.

iE-DAP is a Nod1 agonist. iE-DAP activates NOD1, which in turn activates the NF-κB signaling pathway and MLCK signaling pathway, inducing cellular inflammatory responses and tight junction disruption. iE-DAP downregulates the expression of ZO-1 and Occludin genes. iE-DAP increases the secretion of IL-6, GRO-α, MCP-1, IL-8 and MIP-1β in term human trophoblast cell cultures. iE-DAP triggers preterm birth in pregnant mice, reduces fetal body weight, and induces fetal inflammation. iE-DAP is applicable to research related to mastitis and preterm birth.

NOD2/TLR4 agonist-1 (Compound 2) is a NOD2/TLR4 dual agonist. NOD2/TLR4 agonist-1 lacks immunostimulatory activity and serves as an important negative control in research.

NOD1 agonist-1 is a NOD1 agonist with immunostimulatory and adjuvant activities. NOD1 agonist-1 enhances ovalbumin-specific total IgG antibody responses in mouse vaccination models. NOD1 agonist-1 can be used for the research of immune-related diseases.

NLRP3 agonist 2 (compound 22) is a orally active NLRP3 agonist.NLRP3 agonist 2 activates Caspase-1 in THP1 cells.

Murabutide is an immunomodulator and also a NOD2 receptor agonist. Murabutide enhances the signal transduction of ATR and NOD2, mediates the activation of the DDR pathway, and thereby repairs radiation-induced DNA double-strand breaks. Murabutide inhibits radiation-induced cell apoptosis and protects cells and mice from radiation-induced toxic damage. Murabutide induces the expression and DNA-binding activity of Oct-1 in macrophages, thereby inhibiting the transcription and replication of HIV-1. Murabutide reduces the expression levels of CD4 and CCR5 on the surface of macrophages, and induces the secretion of β-chemokines, TNF-α and IL-6. Murabutide enhances non-specific viral resistance and targets reticuloendothelial cells. Murabutide can be used in research related to radiation-induced damage and human immunodeficiency virus type 1 infection.

TLR7 agonist 27 (compound 24) is a potent TLR7 agonist with an EC₅₀ of 238.1 nM. TLR7 agonist 27 shows weak agonistic activity against NOD2 (nucleotide-binding oligomerization domain 2) (EC₅₀ of 6.2 μM). TLR7 agonist 27 is a potent immunostimulant, and can be used as a vaccine adjuvant and/or immunotherapeutic.

NOD2 agonist 3 (Compound 5) is a potent NOD2 agonist, with an EC₅₀ of 111.45 nM. NOD2 agonist 3 shows immunopotentiating effects.

NOD2 agonist 4 (Compound 12b) is a potent NOD2 agonist with an EC₅₀ of 44.1 nM. NOD2 agonist 4 induces cytokine production (MCP-1, IL-6 and IL-8) in peripheral blood mononuclear cells (PBMCs), both alone and in combination with Lipopolysaccharide (LPS) (HY-D1056). NOD2 agonist 4 can be used for the studies of NOD2-targeted immunomodulator or vaccine adjuvant.

NOD2 agonist 1 (compund 3) is a potent NOD2 agonist (EC50=4.6 nM).