Conduritol B epoxide

Conduritol B epoxide, also known as CBE, is an inhibitor of non-mammalian and mammalian β-glucosidase. When injected in mice it produces the biochemical 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.

Product information

CAS Number: 6090-95-5

Molecular Weight: 162.14

Formula: C6H10O5

Synonym:

Conduritol-B-epoxide

CBE

Conduritol B epoxide

Chemical Name: (1R,2R,3S,4S,5R,6S)-7-oxabicyclo[4.1.0]heptane-2,3,4,5-tetrol

Smiles: O[C@H]1[C@H]2O[C@H]2[C@H](O)[C@@H](O)[C@@H]1O

InChiKey: ZHMWOVGZCINIHW-FTYOSCRSSA-N

InChi: 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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

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.

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).

References:

1. Balreira A, Cavallari M, SaMiranda MC, Arosa FA. Uncoupling between CD1d upregulation induced by retinoic acid and conduritol-B-epoxide and iNKT cell responsiveness. Immunobiology. 2010 Jun;215(6):505-13. doi: 10.1016/j.imbio.2009.07.002. Epub 2009 Aug 3. PubMed PMID: 19651460.
2. Serrano P, Llebaria A, Delgado A. Regio- and stereoselective synthesis of aminoinositols and 1,2-diaminoinositols from conduritol B epoxide. J Org Chem. 2005 Sep 30;70(20):7829-40. Erratum in: J Org Chem. 2006 Jan 6;71(1):448. PubMed PMID: 16277302.
3. Newburg DS, Shea TB, Yatziv S, Raghavan SS, McCluer RH. Macrophages exposed in vitro to conduritol B epoxide resemble Gaucher cells. Exp Mol Pathol. 1988 Jun;48(3):317-23. PubMed PMID: 3371456.

Products are for research use only. Not for human use.