gaucher disease

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.

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

Glucocerebrosides are formed by the tethering of glucose to a ceramide by glucosylceramide synthase. They are present in neuronal and non-neuronal mammalian tissues and are found at low quantities in a large number of plant species. Glucocerebrosides are precursors in the synthesis of lactosylceramides and gangliosides. Increased levels of glucocerebrosides are associated with obesity-induced insulin resistance in mice and with neuronal deficits observed in neuronopathic Gaucher disease. This product is a mixture of glucocerebrosides, with variable ceramide chain lengths, isolated from a spleen of a human with Gaucher's disease.

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.

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.

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

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.

Ibiglustat (Venglustat) succinate is an orally active, brain-penetrant inhibitor of glucosylceramide synthase (GCS). It is utilized in the investigation of Gaucher disease type 3, Parkinson's disease associated with GBA mutations, Fabry disease, GM2 gangliosidosis, and autosomal dominant polycystic kidney disease.

Miglustat (NB-DNJ) is an alkylated product of imino sugar deoxynojirimycin.It is an inhibitor of glucosylceramide synthase, primarily to treat Type I Gaucher disease (GD1).

Eliglustat (Genz 99067) is an oral inhibitor of glucosylceramide synthase which is used in the therapy of type 1 Gaucher disease.

Glucocerebrosidase-IN-1 (compound 11a) hydrochloride is a potent, selective GCase (glucocerebrosidase) inhibitor with IC50 and Ki values of 29.3 μM and 18.5 μM, respectively. It is utilized 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 IC 50 of 29.3 μM and a K i of 18.5 μM. Due to GCase involvement in pathological disorders consequent to enzyme deficiency, Glucocerebrosidase-IN-1 can be used for the research of Gaucher disease (GD) and Parkinson’s disease (PD)[1].

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.

Miglustat-d 9 (hydrochloride), a deuterium-labeled variant of Miglustat (hydrochloride), functions as a glucosylceramide synthase inhibitor. Its primary application is in the treatment of Type I Gaucher disease (GD1) [1][2].

Miglustat hydrochloride (N-Butyldeoxynojirimycin hydrochloride) is an inhibitor of glucosylceramide synthase and can be used for studies about Type I Gaucher disease.

Glucosylceramide synthase-IN-1 (T-036) is a potent, orally active, blood-brain barrier permeable glucosylceramide synthase (GCS) inhibitor that acts on human GCS (IC50: 31 nM) and mouse GCS (IC50: 51 nM). Glucosylceramide synthase-IN-1 can be used to study Gaucher disease.

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.