| Bioactivity | Conduritol B epoxide is an irreversible covalently bound acid β-glucosidase (GCase) inhibitor. | ||||||||||||
| Invitro | Treating N2a and Conduritol B epoxide-N2a cells with G6 gave GC reductions to 7% and 26% of untreated levels, respectively. G6 treated Conduritol B epoxide-N2a also has significantly decreased GS. Co-treatment of G6 and dantrolene of Conduritol B epoxide-N2a cells lead to a similar degree of GC and GS reduction as G6 alone, indicating a specific effect of G6 on inhibition of substrate accumulation, Conduritol B epoxide-N2a cells have higher calcium levels than in N2a cells without caffeine at baseline. Conduritol B epoxide-N2a cells show a significant increase in cytosolic calcium levels compared to N2a cells. Conduritol B epoxide-N2a cells show a significant reduction in OCR as evidenced by approximately 50% in all the parameters, including rate of ATP production, basal respiration, and maximal respiration, compared to N2a cells, indicating reduced mitochondrial function in this nGD cell model. In dantrolene-treated Conduritol B epoxide-N2a cells, levels of Ryr3 are increased to 76% of WT level[1]. | ||||||||||||
| In Vivo | Conduritol B epoxide treatment of 4L, 9H, 9V and WT mice (100 mg/kg/day, i.p.) from postnatal day 5 to 11 does not induce α-synuclein aggregates. Long-term daily Conduritol B epoxide treatment of 4L mice (100 mg/kg/day of Conduritol B epoxide from postnatal day 15 for 24 or 36 doses) leads to hind limb paralysis and small amounts of α-synuclein accumulation in the olfactory bulb, brainstem, and PVP near D3V (dorsal 3rd ventricle)[2]. | ||||||||||||
| Name | Conduritol B epoxide | ||||||||||||
| CAS | 6090-95-5 | ||||||||||||
| Formula | C6H10O5 | ||||||||||||
| Molar Mass | 162.14 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Liou B, et al. Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice. Hum Mol Genet. 2016 Sep 20. pii: ddw322. [Epub ahead of print] [2]. YH Xu, et al. Accumulation and distribution of α-synuclein and ubiquitin in the CNS of Gaucher disease mouse models. Mol Genet Metab. Author manuscript; available in PMC 2012 Apr 1 |