JZ-4109
JZ-4109 is a β-Glucocerebrosidase (GCase) modulator with an IC50 of 8 nM for wild-type recombinant GCase. JZ-4109 binds to an allosteric site at the GCase dimer interface, stabilizes wild-type and GCaseN370S mutant GCase, induces GCase dimerization. JZ-4109 increases GCase protein abundance. JZ-4109 can be used for the research of Parkinson's diseas.
For research use only. We do not sell to patients.
- CAS No.: 1997359-63-3
- Formula: C22H18N4
- Molecular Weight:338.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
JZ-4109 (Compound 3) (0.76 nM-1.56 μM;30 min) potently inhibits wild-type recombinant GCase with an IC50 of 8 nM via linear mixed inhibition[1].
JZ-4109 (0.25-100 μM; heated from 20 °C to 95 °C at 0.1 °C/s) stabilizes wild-type recombinant GCase against thermal denaturation[1].
JZ-4109 (0.2-2 μM; 3 days) significantly increases GCase protein abundance and enzyme activity in healthy control human fibroblast cells without altering GBA mRNA levels[1].
JZ-4109 (2 μM; 3 days) promotes maturation and trafficking of GCase to post-ER compartments in healthy control human fibroblast cells without increasing ER-retained GCase[1].
JZ-4109 (2 μM; 3 days) significantly increases GCase abundance and enzyme activity in lysosomal fractions of HEK cells[1].
JZ-4109 (0.2-2 μM; 3 days) significantly increases mature post-ER GCase protein abundance and enzyme activity in homozygous GBAN370S mutant human fibroblast cells from a type-1 Gaucher’s disease donor[1].
JZ-4109 (4.12-33.0 μM, co-incubated with 16.5 μM GCase) induces dose-dependent dimerization of wild-type GCase in solution[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Healthy control human fibroblast cells
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Concentration:0.2 μM; 2 μM
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Incubation Time:3 days
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Result:Significantly increased GCase protein abundance relative to DMSO control at 0.2 μM.
Produced a greater significant increase in GCase protein abundance relative to DMSO control at 2 μM.
Significantly increased GCase enzyme activity relative to DMSO control at both 0.2 μM and 2 μM.
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Cell Line:HEK cells
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Concentration:2 μM
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Incubation Time:3 days
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Result:Significantly increased GCase levels and enzyme activity in lysosomal enrichment fractions relative to DMSO control.
Showed a significant increase in GCase relative to lysosome marker Lamp1 relative to DMSO control.
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Cell Line:Homozygous N370S mutant human fibroblast cells (type-1 Gaucher’s disease patient)
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Concentration:0.2 μM; 2 μM
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Incubation Time:3 days
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Result:Significantly increased GCase protein abundance and enzyme activity relative to DMSO control at 0.2 μM.
Produced a greater significant increase in GCase protein abundance and enzyme activity relative to DMSO control at 2 μM.
Localized the increase in GCase signal to post-ER mature GCase.
Chemical Information
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CAS No. 1997359-63-3
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Molecular Weight 338.41
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Formula C22H18N4
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SMILES
N1=CC=CC(=C1)C2=NC=3C=CC=CC3C(=N2)NC4CC=5C=CC=CC5C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)