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Chemical Structure| 128446-36-6 Chemical Structure| 128446-36-6

Structure of Methyl-β-cyclodextrin
CAS No.: 128446-36-6

Chemical Structure| 128446-36-6

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Methyl-β-cyclodextrin is a cyclic heptasaccharide that delivers hydrophobic agents by solubilizing non-polar substances. It is also used extensively as a cholesterol-depleting reagent, significantly reducing clathrin-dependent endocytosis and blocking cell migrasome formation.

Synonyms: Methyl-beta-cyclodextrin; Randomly methylated β-cyclodextrin

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Product Citations

Chen, Xi ; Wang, Ya-Juan ; Mu, Tingwei ;

Abstract: Gamma-aminobutyric acid type A receptors (GABAARs) are the major inhibitory neurotransmitter-gated channel in the mammalian central nervous system. GABAARs function as heteropentamers, typically composed of two α1, two β2, and one γ2 subunits. Protein homeostasis between GABAAR folding, trafficking, assembly, and degradation is critical to ensure normal physiological functions. Variants in genes encoded for GABAARs lead to numerous neurological disorders, such as genetic epilepsy with or without neurodevelopmental delay. While these variants are associated with severe clinical presentations of epilepsy, the molecular mechanisms driving the disease remain to be elucidated. In this study, we focused on four missense epilepsy-associated variants (EAVs) in the GABRB2 gene: Q209F210delinsH (c. 627_629del), R240T (c. 719G>C), I246T (c. 737T>C), and I299S (c. 896T>G). HEK293T cells exogenously expressing these β2 variants exhibited significantly reduced GABA-induced peak chloride current, indicating their loss of function. However, the four β2 EAVs differed in the degree of proteostasis deficiencies, including increased ER retention, compromised assembly, decreased protein stability, and reduced trafficking and surface expression, with Q209F210delinsH and R240T variants leading to the most severe degradation. Collectively, these results indicate that these epilepsy-linked variants have debilitating effects on the early biogenesis of the β2 subunit, causing misfolding, aggregation, and rapid degradation before it can be assembled with other subunits and transported to the plasma membrane. Overall, our work offers crucial mechanistic insight into how specific β2 missense variants impact the proteostasis maintenance of GABAARs, which could facilitate the development of effective therapeutics for genetic epilepsy by targeting trafficking-deficient GABAAR variants.

Keywords: GABAA receptor ; GABRB2 ; epilepsy ; missense variants ; proteostasis ; endoplasmic reticulum ; folding ; assembly ; trafficking ; degradation

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Product Details of Methyl-β-cyclodextrin

CAS No. :128446-36-6
Formula : N/A
M.W : 1303.30
SMILES Code : NONE
Synonyms :
Methyl-beta-cyclodextrin; Randomly methylated β-cyclodextrin
MDL No. :MFCD00074980

Safety of Methyl-β-cyclodextrin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H312-H319-H332
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HEK293 cells 2 mM MβCD significantly increased TMEM16A currents J Adv Res. 2020 Sep 15;29:23-32
Escherichia coli MscS in PC10-doped liposomes 750 μM within 90 s Activation of MscS in PC10-doped liposomes, showing lower CD concentration required Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104820118
WT fibroblasts 100 μM 24 hours Increased autophagosome formation but did not block autophagy flux Autophagy. 2017 Aug 3;13(8):1435-1451
NPC1 fibroblasts 100 μM 24 hours Restored impaired autophagy flux in NPC1 cells and reduced cholesterol accumulation Autophagy. 2017 Aug 3;13(8):1435-1451
16HBE cells 1, 5, 7.5 mg/mL 1 hour To investigate the effect of M βCD on hMPV infection, results showed that M βCD significantly reduced hMPV titers in a dose-dependent manner. J Med Virol. 2019 Jun;91(6):949-957
Gly22Ser mutant MscL 5 mM within 90 s Activation of Gly22Ser mutant MscL, showing lower CD concentration required Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104820118
Escherichia coli MscL 25 mM within 90 s Activation of MscL channels, showing CD can activate structurally unrelated mechanosensitive channels Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104820118
Gly113Ala mutant MscS in PE18:1-doped liposomes 5 mM within 90 s Activation of Gly113Ala mutant MscS in PE18:1-doped liposomes, showing lower CD concentration required Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104820118
Escherichia coli MscS in PE18:1-doped liposomes 15 mM within 90 s Activation of MscS in PE18:1-doped liposomes, showing higher CD concentration required Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104820118
Escherichia coli MscS 10 mM within 45 s Activation of MscS channels, mimicking membrane tension Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2104820118
H2228 cells 5 mM 2 hours Cholesterol depletion enhanced LTβR-dependent activation of the NF-κB pathway, manifested by upregulation of NF-κB target gene expression. Cell Commun Signal. 2019 Dec 26;17(1):171
HUVEC cells 5 mM 1 hour Cholesterol depletion potentiated LTβR-dependent activation of the canonical NF-κB pathway, manifested by enhanced degradation of IκBα and increased phosphorylation of RelA. Cell Commun Signal. 2019 Dec 26;17(1):171
A549 cells 5 mM 1 hour Cholesterol depletion potentiated LTβR-dependent activation of the canonical NF-κB pathway, manifested by enhanced degradation of IκBα and increased phosphorylation of RelA. Cell Commun Signal. 2019 Dec 26;17(1):171
Human aortic endothelial cells (HAECs) 10 mM 0–48 h MβCD increased TMEM16A expression in HAECs J Adv Res. 2020 Sep 15;29:23-32
A549 cells (FR-α negative) 5 mM 2 hours Evaluate the effect of FA-M-β-CyD on ATP production. FA-M-β-CyD did not significantly affect ATP production in A549 cells. Int J Nanomedicine. 2017 Apr 28;12:3433-3446
KB cells (FR-α positive) 5 mM 24 hours Evaluate the in vitro cytotoxic activity of FA-M-β-CyD in spheroids of KB cells. FA-M-β-CyD showed potent cytotoxic effects on KB cell spheroids, while M-β-CyD had no such effect. Int J Nanomedicine. 2017 Apr 28;12:3433-3446
human monocyte-derived macrophages (MDMs) 1 mM 30 minutes Used to disrupt lipid rafts, reversing the exNef-induced trained immunity-specific increase in TNF-α production. Cell Rep. 2022 Nov 22;41(8):111674
Caco-2 cells 5 mM 1 hour Inhibition of lipid raft formation, significantly reduced pseudovirion infection J Med Virol. 2023 Jan;95(1):e28266
A549 cells 5 mM 1 hour Inhibition of lipid raft formation, significantly reduced pseudovirion infection J Med Virol. 2023 Jan;95(1):e28266

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c nu/nu mice KB cell xenograft model Intravenous injection 20 mg/kg Single dose, monitored for 42 days Evaluate the in vivo antitumor activity of FA-M-β-CyD in KB cell xenografted mice. FA-M-β-CyD significantly inhibited tumor growth without significant side effects. Int J Nanomedicine. 2017 Apr 28;12:3433-3446

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

0.77mL

0.15mL

0.08mL

3.84mL

0.77mL

0.38mL

7.67mL

1.53mL

0.77mL

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