Conduritol B epoxide

Conduritol B epoxide (CBE) is a mechanism-directed, irreversible, covalent β-glucosidase inhibitor (IC₅₀ = 1 μM) with weak α-glucosidase inhibitory activity (IC₅₀ = 100 μM). Conduritol B epoxide can be used in research on the mechanisms of lysosomal storage disorders and neurodegenerative diseases.

α-glucosidase:100 μM, β-glucosidase:1 μM, Glucocerebrosidase:4.28 - 9.49 μM, Glucocerebrosidase:53 μM (Ki)

Methods: Add 10 μM Conduritol B epoxide to oligodendrocyte cell lines and treat for 72 hours. Perform immunofluorescence staining to assess lysosomal morphology while simultaneously detecting lysosomal substrate accumulation.
Results: Conduritol B epoxide treatment resulted in lysosomal morphological abnormalities and increased lysosomal substrate accumulation, indicating lysosomal dysfunction. [1]

Methods: C57BL/6, CX3CR1⁺/ᴳⱽᴾ (GFP-labeled microglia), and ARE-luc2 (Nrf2 activity reporter) mice aged 15–30 weeks were used. Conduritol B epoxide or PBS (100 mg/kg/day) was administered via intraperitoneal injection for 3 consecutive days.
Results: Glial cells isolated from Conduritol B epoxide-treated mice exhibited altered neuroprotective capacity when co-cultured with neurons. Following Conduritol B epoxide treatment, glial cells isolated from female mice showed significantly reduced ability to induce Nrf2-dependent detoxification pathways in co-cultured neurons. [2]

Cells are homogenized in 1% sodium taurocholate/1% Triton X-100. GCase activity is determined fluorometrically using 4MU-Glucose as the substrate in 0.25% sodium taurocholate, 0.25% Triton X-100 and 0.1M citric-phosphate buffer (pH 5.6). Brain tissues are homogenized in 1X PBS and incubated in 5 μM brain phosphatidylserine and 0.1M citric-phosphate buffer (pH 5.6) for GCase activity assay using 4MU-Glucose as substrate. Protein concentrations are determined by BCA assay using BSA as standard [1].

Gba1 point mutated 4L, 9H and 9V mice or WT mice are intraperitoneally injected with 100 mg/kg/day of Conduritol B epoxide. In short-term experiments, daily injections are initiated at postnatal day 5 and continued for 6 daily doses. The mice are sacrificed on day 12 or 2 months after the last injection. In long-term experiments, 4L mice are injected daily beginning at postnatal day 15 for 24 or 36 daily doses and sacrificed the day after the last injection. Mice are perfused with PBS and organs are harvested for enzyme activity, lipid, and histological analyses [2].

DMSO: 122.5 mg/mL (755.52 mM), Sonication is recommended.

H2O: ≥20 mg/mL (123.35 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 4 mg/mL (24.67 mM), Sonication is recommended.