β-hexosaminidase

M-31850 (1H-Benz[de]isoquinoline-1,3(2H)-dione, 2,2'-(iminodi-2,1-ethanediyl)bis-) 是一种竞争性的 β-己糖胺酶选择性抑制剂，能够抑制人HexA (IC50:6.0 µM) 及HexB (IC50:3.1 µM)。它还能够竞争性抑制 β-N-acetyl-D-hexosaminidaseOfHex2 (Ki:2.5 µM)。

β-N-Acetyl-D-hexosaminidase-IN-1 is a newly discovered chemical compound that acts as an inhibitor for β-N-acetyl-D-hexosaminidase. It exhibits a Ki value of 3.72 μM, indicating its potency in inhibiting the enzyme's activity.

T-5224 是选择性的转录因子c-Fos/activator protein (AP)-1抑制剂，具有抗炎作用，能够特异性抑制 c-Fos/c-Jun 的 DNA 结合活性，但对其他转录因子的结合活性无影响。它抑制 IL-1β 诱导的 Mmp-3、Mmp-13、Adamts-5 转录上调。

β-N-Acetylhexosaminidase 是一种外切糖苷酶，可催化寡糖中末端非还原性 β-N-乙酰半乳糖胺和葡糖胺残基的水解，可用于表观遗传应用。

DNJNAc（亦称 2-Acetamido-1,2-dideoxynojirimycin）是一种高效且特异性的 β-己糖胺酶 (HEX) 抑制剂。HEX 酶催化糖蛋白、神经节苷脂及糖胺聚糖等糖结合物中末端非还原 N-乙酰-β-D-葡萄糖胺 (GlcNAc) 和 N-乙酰-β-D-半乳糖胺 (GalNAc) 的水解。软骨细胞分泌的 HEX 进入细胞外空间，可导致软骨基质降解，使骨关节炎滑液中的 HEX 活性升高。

Z-3578是一种小分子拮抗剂，专门作用于MrgX2 (Mas-related G protein-coupled receptor X2)，具备显著的抗假性过敏功能，KD值为729 nM。Z-3578能有效抑制由substance P (SP)和C48/80诱导的肥大细胞脱颗粒，并减少β-hexosaminidase的释放，其IC50分别为4.90 µM和6.18 µM。同时，它还能显著降低组胺和TNF-α的释放以及细胞内钙流的增加。此外，在小鼠假性过敏模型中，Z-3578有效减轻足部肿胀、染料渗出，并降低血清组胺水平，显示出其良好的体内抗过敏活性。因而，Z-3578有望成为抗过敏特别是针对假性过敏反应的候选化合物。

Clerodendrin (Apigenin-7-O-glucuronopyranosyl(1-2)-glucuronopyranoside) 是一种从 Clerodendron trichotomm 的叶子中分离出一种新的新齿状二萜类化合物，是萝卜锯蝇 Athalia rosae ruficornis 的摄食刺激剂。Clerodendrin 是一种白介素-4 (IL-4) 抑制剂和 β-己糖氨基苷酶 (Hex) 抑制剂。

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 can be used to quantify 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. 4-Methylumbelliferyl-2-acetamido-2-deoxy-β-D-glucopyranoside 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.

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，一种可从肉豆蔻（肉豆蔻科）假种皮分离的天然产品，有能力抑制RBL-2H3细胞内β-己糖胺酶释放，其IC50值为48.4 μM。同样，Maceneolignan A对抗原激活的RBL-2H3细胞中TNF-α释放的抑制作用，其IC50为63.7 μM。

5-Heneicosylresorcinol 对 RBL-2H3 细胞中 β-己糖胺酶的释放具有抑制作用，它还可以防止 3T3-L1 细胞中甘油三酯的积累。它对红线虫、秀丽隐杆线虫和松材线虫具有杀线虫活性，ED50 值分别为 80、30 和 180 ug/mL。

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.