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531660 GCase Activator, NCGC00188758 - Calbiochem

GCase Activator, NCGC00188758 - Calbiochem MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.

Synonyms: N-(4-Ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide, Glucocerebrosidase Activator, Glucocerebrosidase Chemical Chaperone, NCGC758

Primary Target: Glucocerebrosidase (Gcase)
531660
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Overview

Replacement Information

Key Spec Table

Empirical Formula
C₁₇H₁₄N₄O

Products

Catalogue NumberPackaging Qty/Pack
5316600001 Glass bottle 10 mg
Description
OverviewA cell-permeable pyrazolopyrimidine-carboxamide compound that directly binds to glucocerebrosidase (GCase; Kd ~ 9 µM for NT-467 fluorescent labeled GCase) and enhances its activity and serves as a chaperone for its translocation to the lysosomal compartment in fibroblasts of patients with Gaucher disease (AC50 = 5.2 and 6.5 µM for wild type and mutant N370S, respectively). Also shown to be effective in increasing GCase activity in macrophages from Gaucher's disease patients as well as in iPSC-derived macrophages (10.7 and 3.2 fold, respectively). Normalizes reactive oxygen species production and improves chemotaxis in Gaucher disease macrophages. Shown to permeate the blood-brain barrier. Exhibits desirable pharmacokinetic properties with plasma t1/2 = 19.3 h and Cmax of 1.03 µM (following a single injection of 50 mg/kg in mice).

Please note that the molecular weight for this compound is batch-specific due to variable water content.
Catalogue Number531660
Brand Family Calbiochem®
SynonymsN-(4-Ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide, Glucocerebrosidase Activator, Glucocerebrosidase Chemical Chaperone, NCGC758
References
ReferencesAflaki, E., et al. 2014. Sci. Transl. Med. 6, 240ra73.
Patnaik, S., et al. 2012. J. Med. Chem. 55, 5734.
Product Information
FormLight orange powder
Hill FormulaC₁₇H₁₄N₄O
Chemical formulaC₁₇H₁₄N₄O
ReversibleY
Quality LevelMQ100
Applications
Biological Information
Primary TargetGlucocerebrosidase (Gcase)
Purity≥98% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage +2°C to +8°C
Protect from Light Protect from light
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications
Global Trade Item Number
Catalogue Number GTIN
5316600001 04055977259988

Documentation

GCase Activator, NCGC00188758 - Calbiochem SDS

Title

Safety Data Sheet (SDS) 

References

Reference overview
Aflaki, E., et al. 2014. Sci. Transl. Med. 6, 240ra73.
Patnaik, S., et al. 2012. J. Med. Chem. 55, 5734.

Brochure

Title
NPI Flyer- Epigenetics and Nuclear Function Feature
New Products - Antibodies, Small Molecule, Inhibitors

Technical Info

Title
White Paper: Further considerations of antibody validation and usage.
Data Sheet

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision19-December-2014 JSW
SynonymsN-(4-Ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide, Glucocerebrosidase Activator, Glucocerebrosidase Chemical Chaperone, NCGC758
DescriptionA cell-permeable pyrazolopyrimidine-carboxamide that is shown to enhance cellular glucocerebrosidase (GCase) activity in monocyte- & iPSC-derived human macrophage cultures (hMAC & iMAC, respectively) from healthy donors as well as patients with Type I (GCase genotype N370S/N370S or N370S/c.84dupG) or Type II (GCase genotype IVS2+1G>A/L444P) Gaucher disease (GD) due to allosteric modulation of enzyme activity as well as restoration of mutant enzyme lysosomal localization, resulting in greatly enhanced lysosomal GCase substrates processing in GD cultures (%glucosylceremide reduction = 95% in IVS2+1G>A/L444P iMAC, 46.7% in N370S/c.84dupG iMAC, ≥50% in N370S/N370S hMAC & iMAC; %glucosylsphingosine reduction = 80% in IVS2+1G>A/L444P iMAC, ≥33% in N370S/N370S hMAC & iMAC; 8 µM for 6 d). NCGC00188758 treatment is also shown to reactivate ROS production upon phagocytosis of IgG-opsonized erythrocytes in both GD hMAC & iMAC cultures as well as iMAC chemotaxis toward SDF-1. Pharmacokinetic studies reveal good liver and brain exposure following single 50 mg/kg intraperitoneal injection in mice in vivo (Tmax/Cmax/T1/2 = 0.25 h/1.03 µM/19.3 h/plasma, 0.25 h/2.76 µM/18.2 h/brain, 0.25 h/17.29 µM/28.9 h) as well as mouse liver microsome stability (55% degradation in 60 min with NADPH) & Caco-2 permeability (6.0 x 10-6 cm s-1/A to B; 6.0 x 10-6 cm s-1/B to A) in vitro. Unlike the iminosugar-based chemical chaperone Isofagomine, NCGC00188758 does not inhibit GCase activity.
FormLight orange powder
Intert gas (Yes/No) Packaged under inert gas
Chemical formulaC₁₇H₁₄N₄O
Purity≥98% by HPLC
SolubilityDMSO (2.5 mg/ml)
Storage Protect from light
+2°C to +8°C
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Toxicity Standard Handling
ReferencesAflaki, E., et al. 2014. Sci. Transl. Med. 6, 240ra73.
Patnaik, S., et al. 2012. J. Med. Chem. 55, 5734.