| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
TH-237A targets the pathological processes associated with β-amyloid (Aβ) toxicity in Alzheimer's disease. Its primary mechanism of neuroprotection does not involve the stabilization of microtubules, distinguishing it from other paclitaxel derivatives. Unlike the related (R/R) GS-164 stereoisomer, TH-237A does not stimulate tubulin polymerization. Instead, it protects neurons against Aβ-induced neurodegeneration through a distinct pathway. It exhibits high potency with an EC₅₀ of 5 nM, the concentration required to achieve a 50% increase in neuronal survival in the presence of Aβ peptides.
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| ln Vitro |
In vitro, TH-237A demonstrates potent neuroprotective activity. It protects cultured neurons against the toxic effects of β-amyloid (Aβ) with low nanomolar potency. Specifically, exposure of neuronal cultures to Aβ peptide in the presence of 5 nM TH-237A results in a 50% increase in neuronal survival. It was investigated for its effectiveness in protecting neurons against several toxic stimuli. This potent neuroprotection is achieved without relying on microtubule stabilization, a key differentiator from its parent compound paclitaxel and other microtubule-stabilizing agents.
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| ln Vivo |
In vivo, TH-237A has demonstrated significant therapeutic potential in a transgenic mouse model of Alzheimer's disease. In a study using 6 to 10-month old APPsw/PS1dE9 mice, daily subcutaneous administration of TH-237A at 10 mg/kg for 4 months resulted in a significant reduction in Aβ load in the brain. Furthermore, the treatment significantly attenuated the immunoreactivity of IBA-1, a marker for microglia activation, indicating a reduction in neuroinflammation. These results suggest that TH-237A can mitigate Alzheimer's-like neuropathology in vivo. The treatment was well-tolerated, with no difference in body weight gain observed between treated and control mice, suggesting low toxicity from chronic daily administration.
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| Enzyme Assay |
In vitro binding or enzyme assays for TH-237A are not the primary methods for characterizing its activity, as it is a neuroprotective agent rather than a classical enzyme inhibitor. Functional cell-based assays are used to assess its potency. In these assays, primary neuronal cultures are exposed to neurotoxic stimuli such as β-amyloid (Aβ) peptides. The cultures are then treated with varying concentrations of TH-237A, and neuronal survival is quantified. The EC₅₀, the concentration that produces a 50% increase in survival, is calculated from the dose-response curve. These assays are also used to investigate its interaction with the microtubule network.
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| Cell Assay |
In vitro cell-based assays are central to characterizing TH-237A's neuroprotective activity. Primary neuronal cultures are exposed to neurotoxic stimuli, such as β-amyloid (Aβ) peptides, to induce neurodegeneration. These cultures are then treated with varying concentrations of TH-237A, typically in the nanomolar range, to assess its protective effects. Neuronal survival is quantified using standard cell viability assays to determine the compound's potency, such as its EC₅₀ of 5 nM. These studies also investigate its interaction with the microtubule network to confirm its novel, non-stabilizing mechanism of action.
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| Animal Protocol |
In vivo animal studies for TH-237A have been conducted in the APPsw/PS1dE9 transgenic mouse model of Alzheimer's disease. In this established model, TH-237A was administered to 6 to 10-month-old mice via daily subcutaneous injections at a dose of 10 mg/kg body weight for a duration of 4 months. The primary efficacy endpoints included the assessment of Aβ plaque load in the brain via immunohistochemical analysis and the evaluation of microglial activation using the IBA-1 marker. Vehicle-treated littermates were used as controls. Body weight was monitored throughout the study as a general indicator of toxicity.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic (PK) properties of TH-237A, such as half-life and volume of distribution, are not detailed in the available literature. However, the compound is characterized as a brain-penetrant neuroprotective agent, exhibiting favorable permeation across the blood-brain barrier. This key property is essential for its potential to treat central nervous system disorders like Alzheimer's disease. It is soluble in DMSO at 45 mg/mL. For in vivo administration, it can be formulated in a mixture of solvents such as DMSO, PEG300, Tween-80, and saline.
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| Toxicity/Toxicokinetics |
In a chronic 4-month in vivo study in mice, TH-237A was well-tolerated at a dose of 10 mg/kg administered daily via subcutaneous injection. There was no difference in body weight gain between TH-237A-treated mice and vehicle-treated controls, suggesting low toxicity from this treatment regimen. This finding supports a favorable preliminary safety profile for the compound in the context of the study. As a research compound, it is intended for laboratory use only and is not for human therapeutic use.
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| References | |
| Additional Infomation |
TH-237A is a novel, stereochemically defined neuroprotective agent derived from paclitaxel. It is a specific stereoisomer of GS-164 that exhibits potent neuroprotection against Aβ-induced neurodegeneration without stimulating tubulin polymerization. This mechanism is unique and distinguishes it from other microtubule-stabilizing agents used in Alzheimer's disease research. TH-237A is a promising research tool for studying Alzheimer's disease pathology, particularly the role of Aβ toxicity and neuroinflammation. It is not approved for clinical use and is available exclusively for research purposes.
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| Molecular Formula |
C18H17F2NO3
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|---|---|
| Molecular Weight |
333.329292058945
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| Exact Mass |
333.117
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| CAS # |
935467-97-3
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| PubChem CID |
16722711
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
455.5±45.0 °C at 760 mmHg
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| Melting Point |
90 °C (hexane)
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| Flash Point |
229.3±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.626
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
402
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C([C@@]12CO[C@@H](C3C=CC(F)=CC=3)N1[C@@H](C1C=CC(F)=CC=1)OC2)O
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| InChi Key |
AEZQGSQEXPUADE-JWTNVVGKSA-N
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| InChi Code |
InChI=1S/C18H17F2NO3/c19-14-5-1-12(2-6-14)16-21-17(13-3-7-15(20)8-4-13)24-11-18(21,9-22)10-23-16/h1-8,16-17,22H,9-11H2/t16-,17+,18?
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| Chemical Name |
((3R,5S,7as)-3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol.
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| Synonyms |
TH237A; TH 237A; TH237A; mesoGS 164.
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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) |
Ethanol : ~100 mg/mL (~300.00 mM)
DMSO : ≥ 46 mg/mL (~138.00 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.50 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.50 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.50 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0000 mL | 15.0002 mL | 30.0003 mL | |
| 5 mM | 0.6000 mL | 3.0000 mL | 6.0001 mL | |
| 10 mM | 0.3000 mL | 1.5000 mL | 3.0000 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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