Target Validation Information
Target ID T31514
Target Name Lysosomal alpha-glucosidase
Target Type
Clinical Trial
Drug Potency against Target (R)-2,6-Bis-hydroxymethyl-piperidine-3,4,5-triol Drug Info IC50 = 2700 nM [534661]
Alpha-Homonojirimycin Drug Info IC50 = 80 nM [529573]
UNIFLORINE B Drug Info IC50 = 4000 nM [530453]
Alpha-7-Deoxyhomonojirimycin Drug Info IC50 = 19000 nM [526494]
N-adamantanemethyloxypentyl-1-deoxynojirimycin Drug Info IC50 = 400 nM [530471]
2,5-imino-2,5,6-trideoxy-D-manno-heptitol Drug Info IC50 = 7200 nM [534633]
(-)-uniflorine A Drug Info IC50 = 12000 nM [530453]
SALACINOL Drug Info Ki = 970 nM [529528]
Deoxynojirimycin Drug Info IC50 = 130 nM [529573]
Acarbose Drug Info IC50 = 430 nM [552294]
VALIOLAMINE Drug Info IC50 = 18000 nM [529573]
7-O-b-D-Glucopyranosyl-a-homonojirimycin Drug Info IC50 = 380 nM [529573]
Action against Disease Model Acarbose Acarbose attenuates postprandial hyperlipidemia in an intestinal absorptive cell model, Exposure of Caco-2 cells to acarbose at a concentration of 10 mmol/L reduced oleic acid absorption by 30%, triglyceride-rich lipoprotein secretion by around 10%, and apo B-48 secretion by 50%, whereas apo A-I secretion was not affected [552932] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Glycogen storage disease type II (GSDII), caused by a genetic defect in acid alpha-glucosidase (AGLU), leads to a decline in muscle contractility caused by both muscle wasting and a decrease in muscle quality, i.e., force generated per unit muscle mass. A previous study has shown that loss of muscle mass can only explain one-third of the decrease in contractile performance. Here we report on changes in the intramyocellular structural organization in a mouse knockout model (AGLU(-/-) mice) as a possible cause for the decline in muscle quality. Swollen, glycogen-filled lysosomes and centrally localized cores with cellular debris partially contribute to the decline in muscle quality. Altered localization and deposition of cytoskeletal proteins desmin and titin may reflect adaptive mechanisms at the age of 13 months, but a decline in quality at 20 months of age. The early deposition of lipofuscin in AGLU-deficient myocytes (13 months) is most likely a reflection of enhanced oxidative stress, which may also affect muscle quality. These collective findings, on the one hand, may explain the decrease in tissue quality and, on the other, may represent markers for efficacy of therapeutic interventions to restore muscle function in patients suffering from GSDII. [552932]
References
Ref 552932Acarbose attenuates postprandial hyperlipidemia: investigation in an intestinal absorptive cell model. Metabolism. 2009 May;58(5):583-5. doi: 10.1016/j.metabol.2009.02.003.
Ref 534661J Med Chem. 1998 Jul 2;41(14):2565-71.Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.
Ref 529573Bioorg Med Chem. 2008 Aug 1;16(15):7330-6. Epub 2008 Jun 18.In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures.
Ref 530453J Nat Prod. 2009 Nov;72(11):2058-60.Total synthesis of (-)-uniflorine A.
Ref 526494J Nat Prod. 2002 Dec;65(12):1875-81.New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica.
Ref 530471Bioorg Med Chem Lett. 2009 Dec 1;19(23):6600-3. Epub 2009 Oct 8.Synthesis and evaluation of D-gluco-pyranocyclopropyl amines as potential glucosidase inhibitors.
Ref 534633J Nat Prod. 1998 May;61(5):625-8.Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis.
Ref 530453J Nat Prod. 2009 Nov;72(11):2058-60.Total synthesis of (-)-uniflorine A.
Ref 529528J Nat Prod. 2008 Jun;71(6):981-4. Epub 2008 Jun 12.Alpha-glucosidase inhibitor from Kothala-himbutu (Salacia reticulata WIGHT).
Ref 529573Bioorg Med Chem. 2008 Aug 1;16(15):7330-6. Epub 2008 Jun 18.In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures.
Ref 552294Luteolin, a flavone, does not suppress postprandial glucose absorption through an inhibition of alpha-glucosidase action. Biosci Biotechnol Biochem. 2002 Mar;66(3):689-92.
Ref 529573Bioorg Med Chem. 2008 Aug 1;16(15):7330-6. Epub 2008 Jun 18.In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures.
Ref 529573Bioorg Med Chem. 2008 Aug 1;16(15):7330-6. Epub 2008 Jun 18.In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures.

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