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.

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.

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. Upon enzymatic cleavage by β-hexosaminidases, 4-methylumbelliferone (4-μU) is released, and its fluorescence quantifies β-hexosaminidase activity. 4-MU fluorescence is pH-dependent with excitation maxima of 320 and 360 nm at low (1.97-6.72) and high pH (7.12-10.3), respectively, and an emission maximum ranging from 445 to 455 nm, increasing as pH decreases. This compound has been used to quantify β-hexosaminidase activity in serum or leukocytes from patients with GM2 gangliosidoses, such as Tay-Sachs disease, which is characterized by defects in the α subunit of β-hexosaminidase.

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.

T-5224 is a transcription factor c-Fos/AP-1 inhibitor that specifically inhibits the DNA-binding activity of c-Fos/c-Jun without affecting other transcription factors.

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].

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 shows inhibitory effects on the release of β-hexosaminidase from RBL-2H3 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.