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Harmol is a TFEB activator, an orally active monoamine oxidase inhibitor that has anti-tumor, anti-depressant, and anti-aging effects. Harmol can induce cell mitosis, autophagy and apoptosis. Harmol promotes the degradation of α-synuclein through the regulation of the autophagy-lysosomal pathway, improving motor deficits in mouse models of Parkinson's disease.
For research use only. We do not sell to patients.
Harmol is a TFEB activator, an orally active monoamine oxidase inhibitor that has anti-tumor, anti-depressant, and anti-aging effects. Harmol can induce cell mitosis, autophagy and apoptosis. Harmol promotes the degradation of α-synuclein through the regulation of the autophagy-lysosomal pathway, improving motor deficits in mouse models of Parkinson's disease[1][2][3][4].
IC50 & Target
MAO-B
In Vitro
Harmol (3-30 μM, 6-24 h) reduces α-syn levels in PC12 cells in a dose- and time-dependent manner[1].
Harmol (30 μM, 24 h) promotes the nuclear translocation of exogenous TFEB (transcription factor EB) in HeLa cells and enhances the nuclear translocation of endogenous TFEB in N2a cells, along with a restoration of autophagic flux and lysosomal biogenesis[1].
Harmol (0-100 μM, 24 and 48 h) shows time- and dose-dependent inhibition of U251MG cell proliferation and induces cell death[2].
Harmol (0-100 μM, 0-48 h) inhibits the expression of survivin in U251MG cells and promotes the expression of LC3-I and LC3-II proteins, suppressing the Akt/mTOR pathway and inducing cell autophagy and apoptosis[2].
Harmol (0-100 μM, 0-24 h) exhibits slight cytotoxicity in A549 and H226 cells, but shows strong cytotoxicity in H596, inhibiting tumor proliferation[3].
Harmol (60 μM, 3-6 h) enhances the activity of caspase-3, caspase-6, caspase-8, and caspase-9, increases the cleavage of RAPA (an endogenous substrate for caspase-3), inducing apoptosis in H596 cells[3].
Harmol (1.3 μg/mL, 1-3 h) activates autophagy in C2C12 cells[4].
Harmol (1.3 μg/mL, 45-60 min) activates mitochondria-specific autophagy in C2C12 cells, occurring only in inactive TMRM-negative mitochondria[4].
Harmol (1.3 μg/mL, 16 h) upregulates the expression of markers for mitochondrial function in C2C12 cells[4].
Harmol (1.3 μg/mL, 0-20 h) has a specific inhibitory effect on MAO-B[4].
Harmol reduces GABAergic neurotransmission but does not completely inhibit the binding of GABA to GABAARs; GABAAR activity is crucial for Harmol-mediated mitochondrial depolarization and relies on mitochondrial function[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reduced the phosphorylation (p-) and total α-syn levels in PC12 cells in a dose-dependent and time-dependent manner, showing pro-degradation activity between 6 and 24 hours.
Enhanced the LC3B-Ⅱ/LC3B-Ⅰ ratio in PC12 cells, promoted TFEB expression, and increased AMPK phosphorylation at the THr172 site. It facilitated the nuclear translocation of exogenous TFEB in HeLa cells and the translocation of endogenous TFEB to the nucleus in N2a cells. This also increased the expression of the lysosomal marker LAMP1 (lysosomal-associated membrane protein 1) precursor and the mature form of CTSD (cathepsin D).
Showed in C2C12, the protein expression of the mitochondrial transcription and replication factor TFAM and components of complex III (UQCRC2) and complex V (ATP5a) was significantly elevated, along with an increase in polyamine spermidine levels, while DYRK1A phosphorylation remained unchanged.
Showed after 24 hours of treatment, the survival rates of U251MG cells were 102.3%, 99.8%, 93.7%, 82.3%, and 66.7%. After 48 hours of treatment, the survival rates dropped to 98.0%, 93.6%, 72.5%, 38.2%, and 17.3%.
Showed slight cytotoxicity in A549 and H226 cells, while exhibiting strong cytotoxicity in H596.
Showed the activity of caspase-3 and -9 increased in U251MG cells, while there was no significant change in the activity of caspase-8, and a cleaved form of PARP (an endogenous substrate of caspase-3) was detected. There was a dose- and time-dependent inhibition of survivin protein expression. Both LC3-I and LC3-II proteins were expressed, with LC3-II levels increasing over time, indicating that autophagy occurs before apoptosis.
Decreased the phosphorylation of Akt protein in U251MG cells, reduced the level of mTOR phosphorylation (activation), and lowered the expression of p-P70S6K and p-4E-BP1.
Showed in C2C12 cells, aa upregulated LC3 expression, induced PINK1, and activated AMPK.
In Vivo
Harmol (10-40 mg/kg, orally, twice a day for one month) can improve motor deficits, including movement and coordination, in an α-syn transgenic mouse model. It reduces α-syn levels in the substantia nigra and prefrontal cortex and enhances autophagy-mediated degradation of protein aggregates[1].
Harmol (100 mg/kg, administered by gavage, once daily for three weeks) has a mild anxiety-reducing effect in mice[4].
Harmol (100 mg/kg, orally, for three months) improves insulin, glucose homeostasis, and metabolic adaptations in obese mice, with no impact on kidney function[4].
Harmol (15 μg/kg, orally, from day 0 to 50) extends the lifespan of invertebrates[4].
Harmol (100 mg/kg, orally, for two months) delays frailty in aging mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Made mice climb the rod faster, spent more time on the spinning rod, travelled farther in open areas, increased their step frequency and standing posture, reduced posture width, stride, step length, swing, and showed recovery of autonomous movement behavior.
Reduced the expression of α-syn and p62 in the brain’s substantia nigra and prefrontal cortex.
Increased the phosphorylation levels of AMPK Thr172 and TFEB in the substantia nigra, while decreasing the phosphorylation level of mTOR Ser2448.Increased the expression of LC3B-II/LC3B-I, LAMP1, pro-CTSD, and mature ctsd in the substantia nigra, while reducing the expression of p62 and p-ULK1(Ser757)/ULK1.
Showed no change in blood glucose levels, with no change in fasting-mediated ketone body increase, and low permeability of the blood-brain barrier. High levels in the liver and plasma, but low levels in the brain. The mitochondrial autophagy marker PINK1 was elevated, while the phosphorylation levels of AMPK target ACC1 or the autophagy marker LC3-II/LC3-I were unaffected.
Showed no change in the time mice spent in the aversive area (center) versus the non-aversive area (border), with no differences in elevated plus maze tests, and significantly less time spent in the dark/light box.
Increased phosphorylation of ACC2 in the liver and BAT, and levels of the mitochondrial autophagy marker PINK1 were also significantly elevated in the liver, BAT, and soleus.
Reduced the increase in mouse weight, decreased water intake, reduced fat levels, without causing weight loss, lowered fasting blood sugar levels, improved glucose tolerance, and improved insulin resistance without affecting insulin sensitivity. Energy expenditure and oxygen consumption decreased, respiratory quotient remained unchanged, and there were no changes in physical activity. There was less fatty liver, lighter liver weight, and significantly higher levels of serum adiponectin and spermidine in the liver.
Lowered fasting blood sugar, reduced total blood cholesterol, allowed for better coordination during exercise for a longer time, maintained grip strength over time, improved muscle strength, enhanced cardiovascular fitness, produced less lactic acid, and increased total myosin heavy chains.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : 83.33 mg/mL (420.39 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
5.0449 mL
25.2245 mL
50.4490 mL
5 mM
1.0090 mL
5.0449 mL
10.0898 mL
10 mM
0.5045 mL
2.5224 mL
5.0449 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% Corn Oil
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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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