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| Targets |
The primary target of AUTEN-67 is the myotubularin-related phosphatase MTMR14 (also known as JUMPY). It is a specific inhibitor of this enzyme, showing no activity against other phosphatases like CDC25B or PTPN1. The compound binds to MTMR14, inhibiting its phosphatase activity and consequently leading to an induction of autophagic flux. This modulation of autophagy is the key mechanism behind its cellular and neuroprotective effects.
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| ln Vitro |
AUTEN-67 (2-100 µM, 3 hours) induces autophagic flux, increases the survival of HeLa cells, and suppresses MTMR14 by approximately 3%-70% [1]. By inhibiting EDTP, AUTEN-67 (10-100 µM, 2 hours) causes autophagy in Drosophila [1]. In mouse primary neurons, AUTEN-67 (1-50 µM) lowers LC3B-II levels and shields neurons from oxidative stress, increasing cell survival [1].
In vitro, AUTEN-67 (2-100 uM, 3 hours) significantly increases autophagic flux in HeLa cells and specifically inhibits MTMR14 by approximately 3%, 25%, and 70% at concentrations of 2, 10, and 100 uM, respectively. In Drosophila, it induces autophagy via inhibition of EDTP (the fruit fly homolog of MTMR14). In murine primary neurons, it decreases LC3B-II levels and protects cells from oxidative stress, increasing cell viability. |
| ln Vivo |
In zebrafish (10, 50 µM) and mice (i.p. injection of 50 µmol/g body weight), AUTEN-67 increases autophagy[1]. In a mouse model of Alzheimer's disease, AUTEN-67 (19 mg/kg, orally, three times a week for three months) lowers APP levels and recovers nesting behavior[1].
In vivo, AUTEN-67 has shown efficacy in an Alzheimer's disease mouse model. Oral administration (19 mg/kg, 3 times a week for 3 months) restored nesting behavior in the mice by approximately 30%, indicating a positive effect on cognitive function. It also increased autophagic flux in vivo in zebrafish and mice. The compound is orally bioavailable and crosses the blood-brain barrier, making it effective for CNS applications. |
| Enzyme Assay |
The compound's cell-free activity against MTMR14 is determined using a phosphatase activity assay. Recombinant MTMR14 protein is incubated with a generic phosphatase substrate, such as DiFMUP (6,8-difluoro-4-methylumbelliferyl phosphate), which yields a fluorescent product upon dephosphorylation. The reaction is carried out in the presence or absence of AUTEN-67. The IC50 is determined by measuring the reduction in fluorescence, indicating inhibition of MTMR14 activity.
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| Cell Assay |
In cellular assays, HeLa cells are treated with AUTEN-67 at concentrations ranging from 2 to 100 uM for 3 hours. Autophagic flux is measured using a fluorescence-based assay with a reporter such as LC3-GFP (a marker of autophagosomes). An increase in fluorescence indicates enhanced autophagy. MTMR14 inhibition in cells can be assessed by measuring the accumulation of its substrate, phosphatidylinositol 3-phosphate (PI(3)P), via a specific lipid-binding probe.
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| Animal Protocol |
Animal/Disease Models: Alzheimer disease model (Mice expressing the human APP)[1]
Doses: 19 mg/kg, 3 times a week for 3 month Route of Administration: Oral administration Experimental Results: Restored nesting behavior by around 30%. diminished Amyloid β levels in the hemibrain of mice. A protocol for a mouse model of Alzheimer's disease is described. The disease model (e.g., mice expressing the human APP protein) is used. AUTEN-67 is formulated for oral gavage and administered at 19 mg/kg, three times a week, for a period of three months. A behavioral test, such as the nesting behavior assay, is performed to assess cognitive function. At the end of the study, animals are euthanized, and brain tissue is collected to measure levels of disease markers like Amyloid beta peptides. |
| ADME/Pharmacokinetics |
AUTEN-67 is described as an "orally active" autophagy enhancer, indicating it has favorable drug metabolism and pharmacokinetic (DMPK) properties. It can be administered via oral gavage to mice, as in the AD model study. While exact numbers are not provided in the text, the oral formulation (e.g., 19 mg/kg for mice) suggests good bioavailability. Its ability to cross the blood-brain barrier is implied by its efficacy in the AD mouse model (restoring nesting behavior).
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| Toxicity/Toxicokinetics |
Specific toxicology data is not provided, but the compound is described as having "no apparent side effects" in the Alzheimer's disease mouse model. It is generally regarded as well-tolerated at the doses used for research. However, as a modulator of autophagy, a critical cellular process, detailed toxicology studies would be required for therapeutic development. Its current use is exclusively for research purposes. No human clinical trials are reported.
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| References |
[1]. Papp D, et al. AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects. Autophagy. 2016;12(2):273-86.
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| Additional Infomation |
AUTEN-67 is a pioneering chemical tool that specifically targets the MTMR14 phosphatase to enhance autophagy. Its anti-aging and neuroprotective effects make it a candidate for drug discovery in age-related neurodegenerative diseases, including Alzheimer's and Huntington's disease. The compound's ability to improve cognitive symptoms (nesting behavior) in a mouse model of Alzheimer's is a key finding supporting its mechanism of action. It is a research-grade compound and not approved for any clinical indications.
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| Molecular Formula |
C23H14N4O6S
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| Molecular Weight |
474.45
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| Exact Mass |
474.063
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| CAS # |
1783800-77-0
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| Related CAS # |
AUTEN-67 inner salt;301154-74-5
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| PubChem CID |
2324086
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| Appearance |
Orange to red solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
689.7±65.0 °C at 760 mmHg
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| Flash Point |
370.9±34.3 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.755
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| LogP |
3.68
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
992
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(S(NC2=C(N3C=NC4=CC=CC=C43)C(=O)C3=C(C2=O)C=CC=C3)(=O)=O)=CC=C([N+]([O-])=O)C=C1
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| InChi Key |
FSAINSJUQREKEK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H14N4O6S/c28-22-16-5-1-2-6-17(16)23(29)21(26-13-24-18-7-3-4-8-19(18)26)20(22)25-34(32,33)15-11-9-14(10-12-15)27(30)31/h1-13,25H
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| Chemical Name |
N-[3-(benzimidazol-1-yl)-1,4-dioxonaphthalen-2-yl]-4-nitrobenzenesulfonamide
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 2.1077 mL | 10.5385 mL | 21.0770 mL | |
| 5 mM | 0.4215 mL | 2.1077 mL | 4.2154 mL | |
| 10 mM | 0.2108 mL | 1.0539 mL | 2.1077 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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