glucocerebrosidase

Glucocerebrosidase (Glucosylceramidase; GBA), a lysosomal enzyme, catalyzes the hydrolysis of the β-glucosidic linkage in glucocerebroside (GC) to yield glucose and ceramide [1].

Glucocerebrosidase-IN-1 (compound 11a) hydrochloride is a potent and selective glucocerebrosidase (GCase) inhibitor with IC50 of 29.3 μM and Ki of 18.5 μM, used in the research of Gaucher disease (GD) and Parkinson’s disease (PD) [1].

Glucocerebrosidase-IN-1 (compound 11a) is a potent and selective GCase (glucocerebrosidase) inhibitor, with an IC50 of 29.3 μM and a Ki of 18.5 μM. Due to GCase involvement in pathological disorders consequent to enzyme deficiency, Glucocerebrosidase-IN-1 can be used for research of Gaucher disease (GD) and Parkinson's disease (PD)[1].

PFB-FDGlu is a lysosomal Glucocerebrosidase (GCase) substrate with cell-permeable specificity that is cleaved to produce fluorescein.PFB-FDGlu is often used in conjunction with a flow cytometer to measure GCase activity in living cells on an individual cell basis.

NCGC00092410 (ML008) is a glucocerebrosidase (GC) inhibitor with IC50 value of 31 nM. It can be used for the study of Gaucher disease caused by mutation of glucocerebrase gene.

Ambroxol (NA-872) is a secretolytic agent used in the treatment of respiratory diseases associated with viscid or excessive mucus. It is the active ingredient of Mucosolvan, Lasolvan or Mucoangin. The substance is a mucoactive drug with several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of the respiratory tract which play an important role in the body's natural defense mechanisms. It stimulates synthesis and release of surfactant by type II pneumocytes. Surfactants act as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall, in improving its transport and in providing protection against infection and irritating agents.

Ambroxol hydrochloride (Mucosolvan) is a metabolite of BROMHEXINE that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride.

WAY-640509 is a glucocerebrosidase inhibitor.

ML266, a glucocerebrosidase (GCase) chaperone with an IC50 of 2.5 µM, facilitates the transport of the mutant protein to the lysosome, thereby restoring GCase activity without inhibiting the enzyme's function. This compound shows promise for Gaucher disease research.

ML198 is a novel activator and non-inhibitory chaperone of glucocerebrosidase. ML198 serves as a starting point to develop a novel approach towards small molecule treatment for patients suffering from Gaucher disease.

NCGC 607 is a a noninhibitory chaperone of glucocerebrosidase (GCase).

HPSE1-IN-1 (compound 16) functions as a selective Heparanase-1 (HPSE1) inhibitor, displaying moderate activity against exo-β-d-glucuronidase (GUSβ) and glucocerebrosidase (GBA) [1].

13C6 Glucosylsphingosine (d18:1) is an isotopically enriched form of 1-β-D-glucosylsphingosine (d18:1) that is intended for use as an internal standard for the quantification of 1-β-D-glucosylsphingosine by GC- or LC-MS. 1-β-D-Glucosylsphingosine is a lysolipid derivative of glucosylcerebroside that decreases activity of glucocerebrosidase in LA-N-2 cells in a dose-dependent manner.

Glucosylsphingosine (lyso-Gb1), a deacylated glucosylceramide derivative metabolized by glucocerebrosidase, serves as a promising, reliable, and specific biomarker for Gaucher disease monitoring [1].

Therapeutic Agent-1, a heteroaryl compound, serves as an enzyme replacement therapy to enhance glucocerebrosidase activity in the treatment of Gaucher disease [1].

1-β-D-Glucosylsphingadienine is a glucosylsphingosine, which are deacetylated lysolipid derivatives of glucosylcerebrosides . They are formed when sphingosines undergo glucosidation by UDP-glucose. Glucosylsphingosines completely reduce neurite outgrowth and induce death of LA-N-2 cells at concentrations of 10 and 50 μM, respectively. They also decrease the activity of glucocerebrosidase in LA-N-2 cells in a dose-dependent manner. Glucosylsphingosine levels are elevated in patients with Gaucher's disease, both in the spleen (in types 1, 2, and 3) and brain (type 2 and 3); thus, glucosylsphingosine has been used as a key biomarker of the disease. This product contains 1-β-D-glucosylsphingadienine isolated from plants.

C2 Adamantanyl Galactosylceramide (d18:1/2:0) (AdaGalCer) is a bioactive sphingolipid. It reduces globotriaosylceramide 3 synthesis from exogenous lactosylceramide in microsomes. AdaGalCer stimulates recombinant glucocerebrosidase activity in a pH-dependent manner. It activates glucocerebrosidase to decrease glucosylceramide accumulation in fibroblasts and lymphoblasts isolated from patients with Gaucher and Fabry disease, respectively.

HPSE1-IN-2 (compound 2) functions as an inhibitor of Heparanase-1 (HPSE1) while concurrently inhibiting exo-β-d-glucuronidase (GUSβ) and glucocerebrosidase (GBA) activities [1].

Ambroxol acefylline, an active metabolite of the proagent Bromhexine, has potent expectorant effects and functions as a glucocerebrosidase (GCase) chaperone, increasing GCase activity. It induces lung autophagy and has potential applications in Parkinson's disease and neuronopathic Gaucher disease research [1][2].

GCase activator 2 (compound 14), a pyrrolo[2,3-b]pyrazine, is a β-Glucocerebrosidase (GCase) activator (EC50 = 3.8 μM) that induces GCase dimerization (both K-type and V-type) and demonstrates low metabolic clearance in humans and mice [1].

Gcase activator 1 (LTI-291) is a glucocerebrosidase (Gcase) activator.

Sphingomyelins are complex membrane lipids composed of phosphorylcholine, sphingosine, and an acylated group, such as a fatty acid. Lysosphingomyelin is a naturally-occurring lipid which is produced by the removal of the acylated group of sphingomyelin by a deacylase. Lysosphingomyelin may, in turn, serve as a substrate for autotaxin, which removes choline to produce sphingosine-1-phosphate. The receptors and signaling pathways that are activated by lyso-sphingosine are diverse and vary between cell types. Lysosphingomyelin occurs naturally in plasma, is a constituent of lipoproteins, and is increased in some diseases, including dermatitis and Niemann-Pick disease.

Lactosylsphingosine is a bioactive sphingolipid and a form of lactosylceramide that is lacking the fatty acyl group. Lyso-lactosylceramide (1-50 μM) reduces viability of human neutrophils in a concentration-dependent manner. Unlike lactosylceramide,lactosylsphingosine has no effect on protein synthesis and cell proliferation in cardiomyocytes. Lactosylsphingosine is a precursor in the synthesis of lyso-ganglioside GM3.

L-threo Lysosphingomyelin (d18:1) (L-threo-Sphingosylphosphorylcholine) is a naturally occurring bioactive sphingolipid that functions as a potent agonist for S1P receptors, with EC50 values of 19.3, 131.8, and 313.3 nM for hS1P1, hS1P3, and hS1P2, respectively.

Lyso-globotriaosylceramide is a form of globotriaosylceramide that is lacking the fatty acyl group. It binds to Shiga toxin 1 (Stx1) in the presence of cholesterol and phosphatidylcholine but does not bind Stx2. It also reduces viability and aggregation of human neutrophils induced by phorbol 12-myristate 13-acetate when used at concentrations of 50 and 1 μM, respectively. Lyso-globotriaosylceramide accumulates in the brain, heart, kidney, liver, lung, and spleen in a mouse model of Fabry disease, a lysosomal storage disorder characterized by a deficiency in the enzyme α-galactosidase A. It also accumulates in the urine, kidney, and plasma of patients with Fabry disease. Lyso-globotriaosylceramide levels decrease in response to administration of the α-galactosidase inhibitor 1-deoxygalactonojirimycin in a transgenic mouse model of Fabry disease. Decreases in plasma and urine concentrations of lyso-globotriaosylceramide have been used as a biomarker for efficacy of enzyme replacement therapy (ERT) and other therapies in the treatment of Fabry disease.

Lysosphingomyelin is an endogenous bioactive sphingolipid and a constituent of lipoproteins.1,2It is produced by the removal of the acyl group from sphingomyelin by a deacylase and acts as a precursor in the biosynthesis of sphingosine-1-phosphate . D-erythroLysosphingomyelin is an agonist of the S1P receptors S1P1, S1P2, and S1P3(EC50s = 167.7, 368.1, and 482.6 nM, respectively, for the human receptors).3It is also an agonist of the orphan receptor ovarian cancer G protein-coupled receptor 1 (ORG1) that induces calcium accumulation in cells overexpressing OGR1 (EC50= ~35 nM).4Levels of D-erythrolysosphingomyelin are increased in skin isolated from patients with atopic dermatitis, as well as postmortem brain from patients with Niemann-Pick disease type A, but not type B.2,5L-threolysosphingomyelin is also an S1P1-3agonist (EC50s = 19.3, 131.8, and 313.3 nM, respectively).3This product is a mixture of D-erythroand L-threolysosphingomyelin. [Matreya, LLC. Catalog No. 1321] 1.Ito, M., Kurita, T., and Kita, K.A novel enzyme that cleaves the N-acyl linkage of ceramides in various glycosphingolipids as well as sphingomyelin to produce their lyso formsJ. Biol. Chem.270(41)24370-24374(1995) 2.Nixon, G.F., Mathieson, F.A., and Hunter, I.The multi-functional role of sphingosylphosphorylcholineProg. Lipid Res.47(1)62-75(2008) 3.Im, D.-S., Clemens, J., Macdonald, T.L., et al.Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): Structure-activity relationship of sphingosine1-phosphate receptorsBiochemistry40(46)14053-14060(2001) 4.Meyer zu Heringdorf, D., Himmel, H.M., and Jakobs, K.H.Sphingosylphosphorylcholine-biological functions and mechanisms of actionBiochim. Biophys. Acta1582(1-3)178-189(2002) 5.Rodriguez-Lafrasse, C., and Vanier, M.T.Sphingosylphosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type BNeurochem. Res.24(2)199-205(1999)