nod in 1

NOD-IN-1 (Compound 4) is a potent mixed inhibitor of nucleotide-binding oligomerization domain (NOD)-like receptors.

NLRP3-IN-9 (INF-4E) is an inhibitor of NLRP3 ATPase and caspase-1. NLRP3-IN-9 acts by irreversibly trapping thiol nucleophiles, which prevents both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner.

FKGK 18 is an inhibitor of group VIA (GVIA) calcium-independent phospholipase A2 (iPLA2). It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay and is selective for GVIA iPLA2 over GIVA cPLA2 and GV sPLA2 where it shows 80.8 and 36.8% inhibition, respectively. FKGK 18 inhibits iPLA2β activity in cytosolic extracts from INS-1 cells overexpressing iPLA2β (IC50 = ~50 nM) as well as iPLA2γ activity in mouse heart membrane fractions (IC50s = ~1-3 μM). It inhibits glucose-induced increases in prostaglandin E2 production and insulin secretion in human pancreatic islets when used at a concentration of 10 μM and inhibits thapsigargin-induced apoptosis in INS-1 cells overexpressing iPLA2β in a concentration-dependent manner. FKGK 18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice.

AD4, an artemisinin derivative functioning as a proteolytic targeting chimera (PROTAC) for PCLAF, effectively degrades PCLAF in RS4;11 cells with an IC50 of 0.6 nM. This degradation activates the p21 Rb axis, resulting in antitumor activity. Furthermore, AD4 has been demonstrated to prolong survival in NOD SCID mice transplanted with RS4;11 cells, showcasing its in vivo efficacy [1].

GAD65 (524-543) is a biologically active peptide comprising amino acids 524 to 543 of glutamic acid decarboxylase 65 (GAD65). It represents an early islet antigen fragment that elicits proliferative T cell responses in the non-obese diabetic (NOD) mouse model, instrumental in spontaneous autoimmune diabetes research. The peptide serves as a specific, possibly low-affinity stimulant for the diabetogenic T cell clone BDC2.5. Notably, immunization with GAD65 (524-543) heightens NOD mice's vulnerability to type 1 diabetes when subjected to the adoptive transfer of BDC2.5 T cells.

DiaPep277, a 24 amino acid peptide sourced from HSP60 positions 437-460, impedes β-cell destruction in NOD mice and modulates diabetogenic T-cell activity in animal diabetes models [1] [2].

NLRP3-IN-38 (Compound 18) serves as an inhibitor of the NOD-like receptor protein 3 (NLRP3), effectively blocking the activation of the NLRP3 inflammasome with an EC50 value of 23 nM [1].