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Literature summary for 2.4.1.80 extracted from

  • Ashe, K.M.; Budman, E.; Bangari, D.S.; Siegel, C.S.; Nietupski, J.B.; Wang, B.; Desnick, R.J.; Scheule, R.K.; Leonard, J.P.; Cheng, S.H.; Marshall, J.
    Efficacy of enzyme and substrate reduction therapy with a novel antagonist of glucosylceramide synthase for Fabry disease (2015), Mol. Med., 21, 389-399.
    View publication on PubMedView publication on EuropePMC

Inhibitors

Inhibitors Comment Organism Structure
Genz-682452 a mall molecule inhibitor of enzyme GCS, that can traverse the blood–brain barrier. Treating Fabry mice with Genz-682452 results in reduced tissue levels of including globotriaosylceramide and lysoglobotriaosylceramide and a delayed loss of the thermal nociceptive response. Greatest improvements are realized when the therapeutic intervention is administered to younger mice before they developed overt pathology Mus musculus

Organism

Organism UniProt Comment Textmining
Mus musculus O88693
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Mus musculus 129SvEv O88693
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Source Tissue

Source Tissue Comment Organism Textmining
brain
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Mus musculus
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heart
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Mus musculus
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kidney
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Mus musculus
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liver
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Mus musculus
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lung
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Mus musculus
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spleen
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Mus musculus
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Synonyms

Synonyms Comment Organism
GCS
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Mus musculus
glucosylceramide synthase
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Mus musculus

General Information

General Information Comment Organism
malfunction substrate reduction therapy by selectively inhibiting glucosylceramide synthase is used in treatment of Fabry disease, an X-linked inherited glycosphingolipid storage disorder, that is caused by the deficient activity of alpha-galactosidase A, which results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid), leading to kidney, heart, and cerebrovascular disease. Kidneys of both Fabry and wild-type mice treated with enzyme inhibitor GCS Genz-682452 show reductions of galactosylceramide (about 85%) and digalactosylceramide (about 60%), a combination therapy with Genz-682452 and alpha-galactosidase A is more efficacious than either therapy alone at reducing glycosphingolipid levels in Fabry mice, phenotype, overview Mus musculus