1. Neuronal Signaling NF-κB PI3K/Akt/mTOR
  2. Amyloid-β NF-κB mTOR Keap1-Nrf2
  3. TML-6

TML-6, an orally active curcumin derivative, inhibits the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ). TML-6 can upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-oxidative Nrf2 gene. TML-6 has the potential for Alzheimer’s disease (AD) research.

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TML-6 Chemical Structure

TML-6 Chemical Structure

CAS No. : 1462868-88-7

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Based on 1 publication(s) in Google Scholar

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Description

TML-6, an orally active curcumin derivative, inhibits the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ). TML-6 can upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-oxidative Nrf2 gene. TML-6 has the potential for Alzheimer’s disease (AD) research[1].

IC50 & Target[1]

NF-κB

 

mTOR

 

In Vitro

TML-6 (0.65-5.24 µg/mL; for 24 h) reduces the protein expression levels of APP and phospho-NF-κB, and induces the protein expression level of ApoE. TML-6 inhibits the mTOR signaling pathway through the suppression of phospho-mTOR[1].
TML-6 (0.31, 0.63, 2.5, 5, 10, 20 μM; 24 h) reveals no cytotoxicity in Huh-7 cells at concentrations below 5 μM and has an IC50 of 4.19 µg/mL (8 μM)[1].
TML-6 (1.05, 2.09, 3.14, 4.19 μg/mL; 24 h) reduces the production of Aβ40 and Aβ42 between 1.05, 2.09 and 3.14 μg/mL (equal to 2, 4 and 6 μM) in a dose-dependent manner in N2a/APPswe cell[1].
TML-6 can exhibit transcriptional activation of the Nrf2 gene in a dose-dependent manner, with the highest activity at a concentration of 1.32 µg/mL[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: Huh-7 cells
Concentration: 0.65, 1.31, 1.96, 2.61, 3.93, 5.24 µg/mL
Incubation Time: For 24 hours
Result: Reduced the amyloid precursor protein (APP) protein expression level by 60% and decreased the level of phosphorylated NF-κB by about 50% at a dose of 1.96 µg/mL after 24 h treatment.
Induced the protein expression level of ApoE by approximately 44% at a dose of 2.62 µg/mL.
In Vivo

TML-6 (diet; 150 mg/kg/day; for four months) treatment results in significant improvement in learning, suppression of the microglial activation marker Iba-1, and reduction in Aβ in the brain[1].
TML-6 (oral; 150 mg/kg) has a T1/2 of 1.27 hours, a Cmax of 35.9 ng/mL and an AUC of 177 ng•hr/mL[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Six-month-old 3xTg (mutations: APPKM670/671NL, MAPTP301L and PSEN1M146V) AD transgenic mice[1]
Dosage: 150 mg/kg
Administration: Diet; daily; for four months
Result: Improved the learning behaviors, significantly suppressed the Aβ levels and Iba-1 expression in the brain of 3xTg AD transgenic mice.
Animal Model: SD rats[1]
Dosage: 150 mg/kg (Pharmacokinetic Analysis)
Administration: Oral
Result: Had a T1/2 of 1.27 hours, a Cmax of 35.9 ng/mL and an AUC of 177 ng•hr/mL.
Molecular Weight

523.62

Formula

C30H37NO7

CAS No.
Appearance

Solid

Color

Off-white to yellow

SMILES

O=C(N(CC)CC)CC(C)(C(/C=C/C1=CC=C(OC)C(OC)=C1)=O)C(/C=C/C2=CC=C(OC)C(OC)=C2)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility
In Vitro: 

DMSO : 120 mg/mL (229.17 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9098 mL 9.5489 mL 19.0978 mL
5 mM 0.3820 mL 1.9098 mL 3.8196 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Calculation results:
Working solution concentration: mg/mL
Purity & Documentation

Purity: 99.01%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.9098 mL 9.5489 mL 19.0978 mL 47.7445 mL
5 mM 0.3820 mL 1.9098 mL 3.8196 mL 9.5489 mL
10 mM 0.1910 mL 0.9549 mL 1.9098 mL 4.7745 mL
15 mM 0.1273 mL 0.6366 mL 1.2732 mL 3.1830 mL
20 mM 0.0955 mL 0.4774 mL 0.9549 mL 2.3872 mL
25 mM 0.0764 mL 0.3820 mL 0.7639 mL 1.9098 mL
30 mM 0.0637 mL 0.3183 mL 0.6366 mL 1.5915 mL
40 mM 0.0477 mL 0.2387 mL 0.4774 mL 1.1936 mL
50 mM 0.0382 mL 0.1910 mL 0.3820 mL 0.9549 mL
60 mM 0.0318 mL 0.1591 mL 0.3183 mL 0.7957 mL
80 mM 0.0239 mL 0.1194 mL 0.2387 mL 0.5968 mL
100 mM 0.0191 mL 0.0955 mL 0.1910 mL 0.4774 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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