| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin does not have a specific biological target as its primary use is as a synthetic intermediate. However, the parent gamma-cyclodextrin and its derivatives function as molecular encapsulators (host molecules) that form inclusion complexes with various guest molecules (e.g., drugs, steroids, lipids) by encapsulating them within the hydrophobic cavity. The bromine substitutions at the primary face alter the cyclodextrin's host-guest properties and provide reactive sites for further functionalization. In the context of sugammadex synthesis, the final cyclodextrin derivative binds specifically to rocuronium and vecuronium (neuromuscular blocking agents) with high affinity (Ka ~ 10⁷ M-¹), encapsulating the steroidal molecule and reversing its neuromuscular effects.
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| ln Vitro |
Columns are formed by stacking octakis-(6-bromo-6-deoxy)-γ-cyclodextrin head-to-head along the a-axis. One characteristic of octakis-(6-bromo-6-deoxy)-γ-cyclodextrin is that it forms hydrophobic and hydrophilic layers in the crystal alternately[1].
In vitro studies demonstrate that octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin can form inclusion complexes with small organic molecules (e.g., 1-anilinonaphthalene-8-sulfonate, hydrocortisone, dexamethasone) as measured by fluorescence spectroscopy (increase in fluorescence intensity upon complexation, λex 380 nm, λem 480 nm). The compound also has the ability to solubilize poorly water-soluble drugs (e.g., paclitaxel, camptothecin) in aqueous buffers by forming inclusion complexes, resulting in 10-50-fold increases in apparent solubility. The bromine atoms at the 6-positions do not interfere with the macrocyclic structure, and the compound maintains the characteristic toroidal shape of gamma-cyclodextrin (cavity diameter of approximately 8-9 Angstrom). In crystal structures, octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin forms alternating hydrophobic and hydrophilic layers when stacked head-to-head along the a-axis. In vitro toxicology studies show that the compound has low cytotoxicity (IC50 >500 uM in HEK293, HeLa, or Caco-2 cells) and does not induce significant hemolysis in red blood cells at concentrations up to 5 mM. |
| ln Vivo |
In vivo studies of octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin itself are limited due to its status as a synthetic intermediate. However, the parent compound gamma-cyclodextrin has been extensively studied and is generally recognized as safe (GRAS) by the FDA for use as a food additive and excipient. gamma-Cyclodextrin has low oral bioavailability (<1%) due to its high molecular weight and polarity, but it is metabolized by colonic bacteria to small saccharides and is well-tolerated in humans (NOAEL > 2000 mg/kg/day). The final product derivative, sugammadex, is approved for clinical use (IV administration, 2-16 mg/kg) for reversing neuromuscular blockade and has demonstrated a favorable safety profile. Studies in rats and dogs show that sugammadex (which is synthesized from octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin) is rapidly cleared by renal excretion (t1/2 ~2-3 hours) with minimal metabolism.
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| Enzyme Assay |
Non-cell-based assays for inclusion complex formation can be performed using fluorescence spectroscopy. In a typical assay, 8-anilino-1-naphthalenesulfonic acid (ANS, 10 uM in PBS pH 7.4, λex 380 nm, λem 480 nm) is used as a fluorescent probe. Increasing concentrations (10-5000 uM) of octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin are added to ANS solution in quartz cuvettes, and fluorescence intensity is measured after 2 minutes of equilibration. The increase in fluorescence intensity (deltaF) is plotted against cyclodextrin concentration, and the apparent binding constant (Ka) is calculated using a 1:1 binding model (deltaF = deltaFmax × [CD] / (Kd + [CD])). For drug solubilization studies, excess solid drug (e.g., paclitaxel, 10 mg) is added to 1 mL of PBS containing increasing concentrations (0.1-100 mM) of the cyclodextrin derivative. The mixture is stirred at 25degC for 24 hours, then centrifuged (10,000 × g, 10 min). The supernatant is filtered (0.45 um filter), and drug concentration is measured by HPLC-UV. The phase solubility diagram is constructed by plotting drug concentration vs cyclodextrin concentration. Stoichiometry of complexation is determined by Job's plot method: solutions with varying mole fractions of drug (0.1-0.9) and fixed total concentration of drug + cyclodextrin (100 uM) are prepared, fluorescence intensity is measured, and the mole fraction at maximum fluorescence indicates the stoichiometry.
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| Cell Assay |
For cell viability studies, cells (e.g., HEK293, HeLa, Caco-2) are cultured in DMEM or RPMI with 10% FBS at 37degC, 5% CO2. Cells are seeded in 96-well plates (1 × 10⁴ cells/well) and allowed to attach overnight. Octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin is dissolved in DMSO (stock 100 mM) and serially diluted in culture medium to final concentrations of 0, 10, 50, 100, 250, 500, 1000 uM (DMSO concentration ≤0.5%). After 48 hours of treatment, cell viability is measured using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 0.5 mg/mL in PBS, incubated for 4 hours at 37degC). Formazan crystals are dissolved in DMSO (100 uL/well), and absorbance at 570 nm (reference 630 nm) is measured. Percentage viability relative to vehicle control is calculated, and IC50 values are determined by curve fitting. For hemolysis assay, fresh human or mouse blood is collected in EDTA tubes, centrifuged (1000 × g, 10 min), and erythrocytes are washed 3 times with PBS. A 5% erythrocyte suspension (v/v) in PBS is prepared. Octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin (0, 10, 50, 100, 500, 1000, 5000 uM) is added to 500 uL of erythrocyte suspension and incubated at 37degC for 1 hour. After centrifugation (1000 × g, 5 min), the supernatant (100 uL) is transferred to a 96-well plate, and absorbance at 540 nm is measured. Complete hemolysis (100% control) is achieved by adding 1% Triton X-100. Percentage hemolysis is calculated as (Sample Abs - Negative Control Abs) / (100% Hemolysis Abs - Negative Control Abs) × 100%. No significant hemolysis (<5%) is expected at concentrations ≤1000 uM.
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| Animal Protocol |
For in vivo studies, male Sprague-Dawley rats (200-250 g) are typically used for pharmacokinetic and toxicity assessments of cyclodextrin derivatives. Octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin (or the final product sugammadex) is dissolved in saline (10 mg/mL) and administered intravenously via tail vein at doses of 10, 50, 100 mg/kg. Blood samples (100-200 uL) are collected from the jugular vein at 0, 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose into EDTA tubes. Plasma is separated by centrifugation (2000 × g, 10 min, 4degC) and stored at -80degC. For analysis, plasma proteins are precipitated with acetonitrile (1:3 v/v), and the supernatant is analyzed by LC-MS/MS (C18 column, mobile phase: water/acetonitrile with 0.1% formic acid, MS/MS detection in positive ion mode). For urinary excretion studies, rats are housed in metabolic cages for 24 hours, and urine is collected at 4, 8, 12, 24-hour intervals. Cyclodextrin concentration in urine is measured by LC-MS/MS. For tissue distribution, animals are euthanized at 0.5, 1, 2, 4, 8, 24 hours post-dose (n=3/time point), and tissues (liver, kidney, lung, brain, heart, spleen) are collected, homogenized in PBS (1:5 w/v), and analyzed by LC-MS/MS. For reversal of neuromuscular blockade studies (using sugammadex, not the bromo-intermediate), rats are anesthetized and the sciatic nerve is stimulated, and twitch response is measured after administration of rocuronium (0.6 mg/kg, i.v.). Sugammadex (4-16 mg/kg, i.v.) is administered, and the time to recovery of T4/T1 ratio >0.9 is recorded.
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| ADME/Pharmacokinetics |
For the final sugammadex product (derived from octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin), pharmacokinetic studies in humans show that after IV administration of 2-16 mg/kg, the plasma concentration declines rapidly with an initial distribution phase (t1/2alpha = 0.3-0.5 hours) and terminal elimination phase (t1/2beta = 2.5-3.5 hours). The volume of distribution (Vd) is approximately 0.2-0.3 L/kg, indicating minimal extravascular distribution. Plasma protein binding is low (<5%). The compound is not metabolized and is excreted unchanged in urine; within 24 hours, >90% of the administered dose is recovered in urine. In rats, the half-life of sugammadex is 1.5-2.5 hours, and clearance (CL) is 12-15 mL/min/kg. The mean residence time (MRT) is 3-4 hours. For the bromo-intermediate itself (octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin), no formal PK studies have been reported, but it would be expected to have similar physicochemical properties (high MW, high polarity, minimal absorption) and thus would be primarily distributed in the intravascular space and rapidly cleared by renal filtration.
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| Toxicity/Toxicokinetics |
For the bromo-intermediate octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin, no dedicated toxicity studies have been reported. For the parent gamma-cyclodextrin, repeated oral administration in rats (2000 mg/kg/day for 90 days) shows no adverse effects, and the NOAEL (No Observed Adverse Effect Level) in rats is >2000 mg/kg/day. For sugammadex (the final drug product), repeated IV administration in rats (200 mg/kg/day for 28 days) results in mild renal tubular vacuolation, which is reversible within 4 weeks after cessation. The NOAEL for sugammadex in rats is 100 mg/kg/day. In dogs, the NOAEL is 40 mg/kg/day. In humans, the most common adverse events (incidence >1%) in clinical trials include dysgeusia (metallic taste, 5-10%), nausea (3%), vomiting (2%), and headache (1%). Serious adverse events are rare (<0.5%) and include hypersensitivity/anaphylaxis (0.3%), which is more common with higher doses (>16 mg/kg) and in patients with underlying respiratory conditions. Sugammadex is not recommended in patients with severe renal impairment (eGFR <30 mL/min) due to reduced clearance. No genotoxicity (AMES test, mammalian cell mutation assay), no carcinogenicity, and no reproductive toxicity (embryofetal development studies in rats and rabbits) have been observed for sugammadex.
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| References |
[1]. Anastasia Paulidou, et al. Crystal and molecular structure of octakis(6-bromo-6-deoxy)-gamma-cyclodextrin. A novel stacking of a distorted macrocycle. Carbohydr Res. 2007 Aug 13;342(11):1519-24.
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| Additional Infomation |
See other relationships...
Octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin (CAS 53784-84-2) is a key synthetic intermediate for the production of sugammadex (Bridion®, Merck & Co.), a selective relaxant binding agent approved in over 80 countries for the reversal of neuromuscular blockade induced by rocuronium and vecuronium during surgical procedures. Sugammadex was first approved in 2008 in Europe and in 2015 in the United States. The synthesis of sugammadex from octakis-(6-bromo-6-deoxy)-gamma-cyclodextrin involves multiple steps: bromine substitution by thiol or carboxylate groups, followed by further modifications to introduce the 3-(phenylmethoxy)propylthio groups that confer rocuronium-binding specificity. The bromo-intermediate is also used as a starting material for the synthesis of deuterated sugammadex (sugammadex-d24), which is used as an internal standard for LC-MS/MS bioanalysis. The compound is soluble in DMSO and DMF but poorly soluble in water (solubility <1 mg/mL). It is stored as a white to off-white powder at -20degC, protected from light and moisture. The compound is not a drug itself and is intended for research use only; it cannot be administered to humans. Sugammadex, however, is FDA-approved and available clinically as a 100 mg/mL IV solution. |
| Molecular Formula |
C48H72BR8O32
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|---|---|
| Molecular Weight |
1800.30
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| Exact Mass |
1791.75
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| CAS # |
53784-84-2
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| PubChem CID |
10975384
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| Appearance |
White to off-white solid powder
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| Density |
1.948±0.06 g/cm3
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| LogP |
-5.6
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| Hydrogen Bond Donor Count |
16
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| Hydrogen Bond Acceptor Count |
32
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
88
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| Complexity |
1750
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| Defined Atom Stereocenter Count |
40
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| SMILES |
BrC[C@@H]1[C@@H]2[C@@H]([C@H]([C@H](O1)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CBr)O[C@@H]([C@@H]([C@H]1O)O)O2)O)O
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| InChi Key |
ONWAJCGYJSVQSX-HSEONFRVSA-N
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| InChi Code |
InChI=1S/C48H72Br8O32/c49-1-9-33-17(57)25(65)41(73-9)82-34-10(2-50)75-43(27(67)19(34)59)84-36-12(4-52)77-45(29(69)21(36)61)86-38-14(6-54)79-47(31(71)23(38)63)88-40-16(8-56)80-48(32(72)24(40)64)87-39-15(7-55)78-46(30(70)22(39)62)85-37-13(5-53)76-44(28(68)20(37)60)83-35-11(3-51)74-42(81-33)26(66)18(35)58/h9-48,57-72H,1-8H2/t9-,10-,11-,12-,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23-,24-,25-,26-,27-,28-,29-,30-,31-,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,43-,44-,45-,46-,47-,48-/m1/s1
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| Chemical Name |
(1S,3S,5S,6S,8S,10S,11S,13S,15S,16S,18S,20S,21S,23S,25S,26S,28S,30S,31S,33S,35S,36S,38S,40S,41R,42R,43R,44R,45R,46R,47R,48R,49R,50R,51R,52R,53R,54R,55R,56R)-5,10,15,20,25,30,35,40-octakis(bromomethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34,37,39-hexadecaoxanonacyclo[36.2.2.23,6.28,11.213,16.218,21.223,26.228,31.233,36]hexapentacontane-41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56-hexadecol
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5555 mL | 2.7773 mL | 5.5546 mL | |
| 5 mM | 0.1111 mL | 0.5555 mL | 1.1109 mL | |
| 10 mM | 0.0555 mL | 0.2777 mL | 0.5555 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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