β-hexosaminidase

M-31850 (1H-Benz[de]isoquinoline-1,3(2H)-dione, 2,2'-(iminodi-2,1-ethanediyl)bis-) is a potent, selective and competitive β-hexosaminidase (Hex) inhibitor(human HexA and human HexB with IC50s of 6.0 μM and 3.1 μM, respectively). IT also competitively inhibits β-N-acetyl-D-hexosaminidase OfHex2 with a Ki of 2.5 μM.

β-N-Acetyl-D-hexosaminidase-IN-1 is a newly discovered chemical compound that inhibits β-N-acetyl-D-hexosaminidase, exhibiting a Ki value of 3.72 μM, which indicates its potency in inhibiting the enzyme's activity.

T-5224 is a selective inhibitor of the transcription factor c-Fos/activator protein (AP)-1 with anti-inflammatory effects. T-5224 specifically suppresses the DNA-binding activity of c-Fos/c-Jun, thereby inhibiting IL-1β-induced transcriptional upregulation of Mmp-3, Mmp-13, and Adamts-5, without affecting the binding activity of other transcription factors. T-5224 can be used in research on rheumatoid arthritis, osteoarthritis, and cartilage degeneration.

Mudanpioside E is a paeoniflorin-type monoterpenoid glycoside naturally found in plants of the Paeoniaceae family. Mudanpioside E is an orally active antiallergenic agent that inhibits IgE-mediated β-hexosaminidase release (IC₅₀ = 40.34 μM). Mudanpioside E can reverse the inhibitory effect of Xiao Qing Long Tang extract, a formulation containing Paeonia lactiflora root, on passive cutaneous anaphylaxis in mice, making it suitable for research on allergic diseases.

β-N-Acetylhexosaminidase, an exoglycosidase, catalyzes the hydrolysis of terminal non-reducing β-N-acetylgalactosamine and glucosamine residues in oligosaccharides for epigenetic applications [1].

DNJNAc, also known as 2-Acetamido-1,2-dideoxynojirimycin, is a highly potent and specific inhibitor of β-hexosaminidase (HEX). HEX enzymes catalyze the hydrolysis of terminal non-reducing N-acetyl-β-D-glucosamine (GlcNAc) and N-acetyl-β-D-galactosamine (GalNAc) residues from glycoconjugates such as glycoproteins, gangliosides, and glycosaminoglycans. HEX secreted by chondrocytes into the extracellular space contributes to cartilage matrix degradation, and HEX activity is elevated in the synovial fluid of osteoarthritis patients.

Z-3578 is a small molecule antagonist targeting the MrgX2 (Mas-related G protein-coupled receptor X2) with notable anti-pseudoallergic properties, exhibiting a KD value of 729 nM. It effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, with IC50 values of 4.90 µM and 6.18 µM, respectively, suppresses the release of β-hexosaminidase, and significantly reduces the release of histamine and TNF-α, as well as intracellular calcium flux. Additionally, in a mouse pseudoallergy model, Z-3578 significantly alleviates foot swelling, dye leakage, and reduces serum histamine levels, indicating a strong in vivo anti-allergic effect. Z-3578 presents as a promising lead compound in the field of anti-allergic treatments, particularly for pseudoallergic reactions.

MRS2690 disodium is a selective agonist of the P2Y14 receptor. It inhibits adenylyl cyclase activity, thereby reducing intracellular cAMP levels and causing concentration-dependent vasoconstriction in porcine coronary arteries. MRS2690 disodium induces intracellular calcium mobilization, activates P38, and stimulates [35S]GTPγS binding on the membrane of RBL-2H3 cells. It also enhances the β-hexosaminidase (β-Hex) release induced by antigen (NP-BSA) and C3a. This compound is useful for research in ischemic heart disease.

XAT-13 is an orally active antiallergic agent that binds to the active pocket of MRGPRX2, inhibiting calcium influx (Calcium influx) and β-hexosaminidase release induced by C48/80. It is applicable for research in pseudo-allergic reactions.

Clerodendrin (Apigenin-7-O-glucuronopyranosyl(1-2)-glucuronopyranoside) is a new neodentate diterpenoid isolated from the leaves of Clerodendron trichotomm, a radish sawfly Athalia Clerodendrin is an interleukin-4 (IL-4) inhibitor and β-hexosaminidase (Hex) inhibitor.

4-Methylumbelliferyl-2-acetamido-2-deoxy-β-D-Glucopyranoside is a fluorogenic substrate for β-hexosaminidases that releases fluorescent 4-methylumbelliferone upon enzymatic cleavage, enabling sensitive quantification of enzyme activity across pH-dependent excitation and emission ranges, and is extensively used in clinical and research assays for GM2 gangliosidoses such as Tay-Sachs disease.

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg/ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g/animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

Ganglioside GM2 asialo (asialo- GM2) is a glycosphingolipid containing three monosaccharide residues and a fatty acid of variable chain length but lacking the sialic acid residue present on ganglioside M2. Asialo-GM2 levels are low-to-undetectable in normal human brain, but it accumulates in the brain of patients with Tay-Sachs and Sandhoff disease, which are neurodegenerative disorders characterized by deficiency of lysosomal β-hexosaminidase A and B, respectively. It also binds to various bacteria, including Pseudomonas isolates derived from cystic fibrosis patients. Asialo-GM2 mixture contains ganglioside GM2 asialo molecular species with fatty acyl chains of variable lengths.

Variegatic acid is a natural inhibitor of β-hexosaminidase release and tumor necrosis factor (TNF)-α secretion from rat basophilic leukemia (RBL 2H3) cells, with IC50 values of 10.4 μM and 16.8 μM, respectively, also inhibiting PKC β1 activity with an IC50 value of 36.2 μM.

Maceneolignan A, a natural product isolated from the aril of Myristica fragrans (Myristicaceae), inhibits β-hexosaminidase release in RBL-2H3 cells, exhibiting an IC50 of 48.4 μM. Additionally, it suppresses TNF-α release in antigen-stimulated RBL-2H3 cells with an IC50 of 63.7 μM [1].

MEDI4212 is a humanized IgG1λ monoclonal antibody inhibitor targeting IgE. It effectively inhibits human IgE-mediated functional responses, such as calcium signaling, β-hexosaminidase release, and phagocytosis, through its receptor FcεRI. MEDI4212 prevents IgE from binding to CD23 with an IC50 of 8 nM and can be utilized in severe asthma research.

Dichotomine C ((R)-(-)-Dichotomine C) is a β-carboline alkaloid with anti-allergic properties. It inhibits the release of β-hexosaminidase from RBL-2H3 cells with an IC50 of 62 μM. Additionally, it suppresses antigen IgE-mediated release of TNF-α and IL-4 in RBL-2H3 cells, with IC50 values of 19 μM and 15 μM, respectively. This compound is applicable in the research of type I hypersensitivity reactions.

5-Heneicosylresorcinol shows inhibitory effects on the release of β-hexosaminidase from RBL-2H3 cells, it also prevents triglyceride accumulation in 3T3-L1 cells. 5-Heneicosylresorcinol has nematicidal activity against nematodes Panagrellus redivivus, Cae

5-Nonadecylresorcinol is a natural alkylresorcinol isolated from wheat bran. This product exhibits significant anti-degranulation activity in the RBL-2H3 cell model, effectively inhibiting DNP-BSA-induced release of β-hexosaminidase. It shows no cytotoxicity at experimental concentrations and serves as a pharmacological tool for researching natural anti-allergic agents and their mechanisms in mast-cell-like cells.

Thujopsene, a sesquiterpene found in T. dolabrata, exhibits a wide range of biological activities. It inhibits Na+/K+-ATPase and cytochrome P450 (CYP) isoform CYP2B6 with IC50 values of 25.9 µg/ml and Ki of 0.8 µM, respectively. Additionally, thujopsene demonstrates antimicrobial efficacy against both Gram-positive and Gram-negative bacteria, such as S. aureus, M. luteus, and S. typhimurium, with MICs ranging from 25-50 µg/ml. It also suppresses antigen-induced β-hexosaminidase release in IgE-sensitized RBL-2H3 mast cells (IC50= 25.1 µM) and shows cytotoxicity against A549 non-small cell lung cancer cells with an LC50 of 35.27 µg/ml. Furthermore, thujopsene causes mortality in mites D. farinae and T. putrescentiae, with LC50s of 9.82 and 10.92 µg/cm2, respectively.