- Scyllo-Inositol targets α-Synuclein, specifically inhibiting its aggregation and seeding activity. The EC50 value for inhibiting α-Synuclein fibril formation was reported to be approximately 5 mM. [1]

- Scyllo-Inositol dose-dependently inhibited the aggregation of recombinant α-Synuclein monomers: at concentrations of 1 mM, 5 mM, and 10 mM, it reduced fibril formation by ~30%, ~70%, and ~90%, respectively, as measured by Thioflavin T (ThT) fluorescence assay. [1]
- The drug blocked α-Synuclein "seeding" activity: pre-incubation of α-Synuclein seeds with 5 mM Scyllo-Inositol reduced the ability of seeds to induce aggregation of soluble α-Synuclein by ~85%, as confirmed by both ThT fluorescence and negative-stain transmission electron microscopy (TEM). [1]
- In α-Synuclein-overexpressing neuroblastoma cells, treatment with 10 mM Scyllo-Inositol for 48 hours decreased intracellular α-Synuclein oligomer and fibril levels by ~60% (detected via immunoblotting with oligomer-specific antibodies) and improved cell viability by ~40% (measured via MTT assay) compared to untreated cells. [1]

- α-Synuclein Fibril Formation Inhibition Assay: Recombinant α-Synuclein monomers (20 μM) were incubated with different concentrations of Scyllo-Inositol (0–10 mM) in buffer at 37°C with constant shaking (200 rpm). At 24-hour intervals, 10 μL of the reaction mixture was mixed with ThT solution (50 μM final concentration), and fluorescence intensity (excitation: 440 nm, emission: 480 nm) was measured to quantify fibril formation. [1]
- α-Synuclein Seeding Activity Block Assay: Pre-formed α-Synuclein seeds (5 μM) were incubated with 5 mM Scyllo-Inositol for 2 hours at 37°C. The mixture was then added to soluble α-Synuclein monomers (20 μM), and fibril formation was monitored via ThT fluorescence for 72 hours. Negative-stain TEM was also used to visualize fibril morphology at the end of incubation (samples were stained with uranyl acetate and imaged at 80 kV). [1]

- α-Synuclein Overexpressing Neuroblastoma Cell Assay: Neuroblastoma cells stably expressing human α-Synuclein (wild-type) were seeded in 96-well plates (1×10⁴ cells/well) and cultured for 24 hours. Scyllo-Inositol was added to the medium at final concentrations of 1 mM, 5 mM, and 10 mM, and cells were incubated for 48 hours. For intracellular α-Synuclein detection: cells were fixed, permeabilized, and stained with α-Synuclein oligomer-specific primary antibodies and fluorescent secondary antibodies, then imaged via confocal microscopy to quantify oligomer puncta. For cell viability: MTT reagent was added to wells, incubated for 4 hours, and absorbance at 570 nm was measured to calculate viability relative to untreated controls. [1]

Absorption, Distribution and Excretion
Inositol is absorbed via the small intestine. In patients with inositol deficiency, peak plasma concentrations occur at 4 hours after oral administration. Inositol is absorbed by tissues via a sodium-dependent inositol cotransporter, which also participates in glucose absorption. The maximum plasma concentration of inositol after oral administration can reach 36-45 μg. Most of the administered dose is excreted in the urine. Pharmacokinetic studies of inositol in preterm infants suggest an estimated volume of distribution of 0.5115 L/kg. Pharmacokinetic studies of inositol in preterm infants suggest an estimated clearance of 0.0679 L/kg/h. Metabolism/Metabolites Inositol is thought to be metabolized to phosphoinositol, which is then converted to phosphatidylinositol-4,5-bisphosphate, a precursor to a second messenger molecule. Inositol can be converted to D-chiral inositol by epimerase activity. Normal modifications to the inositol structure appear to exist across all the different isomers.

---

Biological half-life>
The pharmacokinetic characteristics of inositol in preterm infants were studied, and the elimination half-life was estimated to be 5.22 hours.

Protein Binding
It is believed that inositol can bind to plasma proteins.

[1]. α-Synuclein aggregation, seeding and inhibition by scyllo-inositol. Biochem Biophys Res Commun. 2016 Jan 15;469(3):529-34.

Inositol is an inositol with the inositol-configuration. It functions as a compatibility osmotic regulator, a nutrient, an EC 3.1.4.11 (phosphatidylinositol phospholipase C) inhibitor, a human metabolite, a Daphnia magna metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, and a mouse metabolite. Inositol is an isomer of glucose and has traditionally been considered a B vitamin, but its status as a vitamin is uncertain, and no deficiency has been found in humans. (From Martindale, The Extra Pharmacopoeia, 30th edition, p. 1379) Inositol phospholipids play an important role in signal transduction. Inositol has been investigated for the treatment of Alzheimer's disease. Inositol is a collection of nine different stereoisomers, but usually refers only to the most common type of inositol—inositol. Inositol is cis-1,2,3,5-trans-4,6-cyclohexanehexanol, prepared by precipitation and hydrolysis of crude phytic acid in a water extract of corn kernels. These molecules are structurally similar to glucose and are involved in cell signaling. It is considered a pseudovitamin because it does not meet the criteria for an essential vitamin; although it is vital in the body, a deficiency of this molecule does not cause disease. Inositol was once listed as an ingredient in over-the-counter medications by Health Canada, but all products with inositol as a primary ingredient have been discontinued. Under the U.S. Food and Drug Administration (FDA), inositol is listed as a Generally Recognized As Safe (GRAS) substance. D-chiral inositol is being investigated in the clinical trial NCT03201601 (evaluating the efficacy of an inositol:D-chiral inositol 3.6:1 mixture in women with polycystic ovary syndrome). Inositol is a metabolite found in or produced by Escherichia coli (K12 strain, MG1655 strain). Inositol is a metabolite found in or produced by Escherichia coli (K12 strain, MG1655 strain). It has also been reported to be present in tea trees, apple trees, and other organisms with relevant data. Coconut alcohol, a stereoisomer of inositol, is a plant sugar alcohol primarily found in coconut trees and possesses potential amyloid activity. It exhibits plaque formation inhibitory activity. After oral administration, coconut alcohol can cross the blood-brain barrier and inhibit the formation of β-amyloid plaques in the brain through an undefined mechanism. This may help slow disease progression and improve cognitive function in Alzheimer's patients. Inositol is a natural sugar found in cell membrane phospholipids, plasma lipoproteins, and the cell nucleus (in phosphate form), possessing potential chemopreventive properties. As one of many intracellular phosphorylated compounds, inositol participates in cell signaling and may stimulate tumor cell differentiation. (NCI04) D-chiral inositol, an isomer of inositol, may be used to improve insulin sensitivity and reproductive function. Oral administration of D-chiral inositol can improve insulin sensitivity, enhance glucose tolerance, affect reproductive hormones and function, and may regulate certain neurotransmitters. Inositol is a metabolite of Saccharomyces cerevisiae. Pharmacological Indications: Inositol can be used in unlimited quantities in food. As a drug, inositol can be used as a nutritional supplement in special dietary foods and infant formula. Because inositol plays an important role in ensuring egg fertilization, its application in the treatment of polycystic ovary syndrome (PCOS) has been investigated. Inositol is currently being investigated for the treatment of diabetes, prevention of metabolic syndrome, weight loss assistance, treatment of depression, mental illness and anxiety, and cancer prevention. Mechanism of Action: The mechanism of action of inositol in brain diseases is not fully understood, but it is generally believed that it may be involved in the synthesis of neurotransmitters and is a precursor to the phosphatidylinositol cycle. Changes occurring in this cycle mimic the situation where postsynaptic receptors are activated but not truly activated. This activity triggers a pseudoactivation, thereby modulating the activity of monoamines and other neurotransmitters. Reports indicate that insulin resistance plays a crucial role in the clinical development of polycystic ovary syndrome (PCOS). Hyperinsulinemia can induce excessive androgen production by stimulating the ovaries to produce androgens and reducing serum levels of sex hormone-binding globulin. One mechanism of insulin deficiency is thought to be related to the lack of inositol in inositol phosphopolysaccharides. Inositol supplementation can enable it to act as a direct messenger of insulin signaling and improve tissue glucose uptake. This mechanism is thought to be related to the role of inositol in diabetes treatment, metabolic syndrome, and weight loss. In cancer, the mechanism of action of inositol is not fully elucidated. It is hypothesized that inositol supplementation can increase the level of low-phosphate inositol phosphate, thereby affecting cell cycle regulation, growth, and differentiation of malignant cells. On the other hand, inositol hexaphosphate, formed after inositol administration, exhibits antioxidant properties by chelating iron ions and inhibiting hydroxyl radicals.

---

- Mechanism of action: Inositol binds to α-synuclein monomers and early oligomers (confirmed by surface plasmon resonance (SPR), with a binding affinity (KD) of approximately 1.2 mM), preventing them from assembling into toxic fibers and blocking the spread of α-synuclein seeds (a key process in synucleinogenic diseases such as Parkinson's disease). [1]
- Background: This study focuses on inositol as a potential therapeutic agent for synucleinogenic diseases, as the abnormal aggregation of α-synuclein is a pathological marker of these diseases, such as Parkinson's disease and multiple system atrophy. [1]

C6H12O6

180.1559

180.063

488-59-5

892

White to off-white solid powder

2.0±0.1 g/cm3

291.3±40.0 °C at 760 mmHg

350ºC

143.4±21.9 °C

0.0±1.4 mmHg at 25°C

1.784

-2.11

6

6

0

12

104

0

CDAISMWEOUEBRE-UHFFFAOYSA-N

InChI=1S/C6H12O6/c7-1-2(8)4(10)6(12)5(11)3(1)9/h1-12H

cyclohexane-1,2,3,4,5,6-hexol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~5 mg/mL (~27.75 mM)

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 Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

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
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)