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Purity: ≥98%
Conduritol B epoxide (formerly known as CBE) is an irreversible/covalent inhibitor of non-mammalian and mammalian β-glucosidase (GCase). β-glucosidase catalyzes the hydrolysis of the glycosidic bond to terminal non-reducing residues in β-D-glucosides and oligosaccharides, with release of glucose. When injected in mice it produces the bioactive compound and certain clinical and pathological characteristics of Gaucher disease. Conduritol B epoxide is a mechanism-based inhibitor which binds covalently to the catalytic site of acid β-glucosidase.
| Targets |
GCase/acid β-glucosidase
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|---|---|
| ln Vitro |
G6 treatment decreased GC to 7% and 26% of untreated levels in N2a and Conduritol B Epoxide-N2a cells, respectively. Conduritol B Epoxide-N2a treated with G6 likewise demonstrated a markedly lower GS. In comparison to untreated levels, the GC of Conduritol B Epoxide-N2a cells was decreased to 7% and 26%, respectively. A comparable level of GC and GS decrease was observed upon co-treatment of G6 and dantrolene as compared to G6 alone, suggesting that G6 has a distinct effect on preventing substrate accumulation. Cytoplasmic calcium levels were considerably greater in Conduritol B epoxy-N2a cells compared to N2a cells. Conduritol B epoxy-N2a cells had higher calcium levels than baseline caffeine-calibrated N2a cells. lowered mitochondrial function in this nGD cell type was indicated by the OCR of Conduritol B epoxy-N2a cells, which was much lower than that of N2a cells. All parameters, including ATP generation rate, basal respiration, and maximal respiration, were lowered by roughly 50%. Ryr3 levels rose to 76% of WT levels in Conduritol B epoxy-N2a cells treated with dantrolene [1].
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| ln Vivo |
Following treatment from postnatal days 5 to 11, 4L, 9H, 9V, and WT mice do not develop α-synuclein aggregates in response to conduritol B epoxide (100 mg/kg/d, i.p.). When given 24 or 36 times a day starting on day 15 after birth, Conduritol B epoxide (100 mg/kg/d) caused hindlimb paralysis in 4L mice and reduced levels of α-synuclein in the brainstem and olfactory bulb. and buildup at the PVP close to the dorsal third ventricle, or D3V [2].
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| Enzyme Assay |
GCase enzyme activity[2]
For GCase activities, tissues (∼50 mg) were homogenized [1:10 (mg: μl) in 1% sodium taurocholate/Triton-X100 (TC/TX), sonicated (4°C, 30s × 3), and clarified (10,000×g; 5 min, 4°C). The assay mixtures were pre-incubated in the presence or absence of conduritol B epoxide (CBE) (1 mM; 30 min at room temperature), and then substrate (4MU-Glc) was added and incubated (1 h, 37°C). Protein concentrations were determined using the BCA kit according to manufacturer's instructions. |
| Cell Assay |
Cell culture and treatment[1]
N2a cells were maintained in DMEM/10% FBS medium. Neuronal differentiation of N2a was carried out in the differentiation medium containing 0.5% FBS, 10 µM retinoic acid, 50 ng/ml GDNF and 1 mM dbcAMP in DMEM for 3 days. The differentiated N2a cells were treated with 2 mM conduritol B epoxide (CBE) for 5 days in the differentiation medium. Dantrolene (12.5 µM), ryanodine (10 µM) or G6 (0.8 µM) was added to the CBE-N2a cells and cultured for 5 days. The medium with the reagents was changed every 2 days. The differentiation status of the neuronal cells was confirmed by anti-Map2 (mature neuron) or anti-Nestin (undifferentiated neuronal cells) antibody staining. Cell viability after each drug treatment was measured by CellTiter-FluorTM Cell Viability assay. The dose for each compound was determined from CellTiter-FluorTM Cell Viability assay with >95% viability and endotoxin test of <0.05 EU/ml. The cells were from same passage and treated at the same time for all the experiments. |
| Animal Protocol |
conduritol B epoxide (CBE)-treated mice[2]
Gba1 point mutated 4L, 9H and 9V mice or WT mice were intraperitoneally injected with 100 mg/kg/day of conduritol B epoxide (CBE). In short-term experiments, daily injections were initiated at postnatal day 5 and continued for 6 daily doses. The mice were sacrificed on day 12 or 2 months after last injection. In long-term experiments, 4L mice were injected daily beginning at postnatal day 15 for 24 or 36 daily doses and sacrificed the day after last injection. Mice were perfused with PBS and organs were harvested for enzyme activity, lipid and histological analyses. |
| References |
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| Additional Infomation |
1-D-1,2-anhydro-myo-inositol is a conduritol epoxide resulting from the formal epoxidation of the double bond of (+)-conduritol B. It has a role as an EC 3.2.1.48 (sucrose alpha-glucosidase) inhibitor and an EC 3.2.1.10 (oligo-1,6-glucosidase) inhibitor. It is functionally related to a (+)-conduritol B. It is an enantiomer of a 1-L-1,2-anhydro-myo-inositol.
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| Molecular Formula |
C6H10O5
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|---|---|
| Molecular Weight |
162.141
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| Exact Mass |
162.052
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| Elemental Analysis |
C, 44.45; H, 6.22; O, 49.34
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| CAS # |
6090-95-5
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| Related CAS # |
6090-95-5;
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| PubChem CID |
119054
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| Appearance |
White to off-white solid powder
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| Density |
1.9±0.1 g/cm3
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| Boiling Point |
360.5±42.0 °C at 760 mmHg
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| Melting Point |
157-159ºC
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| Flash Point |
171.8±27.9 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.732
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| LogP |
-0.49
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
11
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| Complexity |
154
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| Defined Atom Stereocenter Count |
6
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| SMILES |
[C@@H]1([C@@H]([C@H]([C@H]2[C@@H]([C@@H]1O)O2)O)O)O
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| InChi Key |
ZHMWOVGZCINIHW-FTYOSCRSSA-N
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| InChi Code |
InChI=1S/C6H10O5/c7-1-2(8)4(10)6-5(11-6)3(1)9/h1-10H/t1-,2-,3+,4+,5-,6+/m0/s1
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| Chemical Name |
(1R,2R,3S,4S,5R,6S)-7-oxabicyclo[4.1.0]heptane-2,3,4,5-tetrol
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| Synonyms |
Conduritol B epoxide; conduritol b epoxide; 6090-95-5; 1,2-Anhydro-myo-inositol; (1r,2r,3s,4s,5r,6s)-7-oxabicyclo[4.1.0]heptane-2,3,4,5-tetrol; (1R,2R,3S,4S,5R,6S)-7-Oxabicyclo[4.1.0]heptane-2,3,4,5-tetraol; myo-Inositol, 1,2-anhydro-; CHEMBL291020; CHEBI:67233; Conduritol-B-epoxide; CBE
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~616.75 mM)
DMSO : ~50 mg/mL (~308.38 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (15.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (15.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (15.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (616.75 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.1675 mL | 30.8375 mL | 61.6751 mL | |
| 5 mM | 1.2335 mL | 6.1675 mL | 12.3350 mL | |
| 10 mM | 0.6168 mL | 3.0838 mL | 6.1675 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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