| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Kd: 89 uM (TDP-43102–269)[1]
rTRD01 targets TDP-43 (TAR DNA-binding protein 43), a protein involved in RNA processing and metabolism that is implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The compound binds to TDP-43's RRM1 and RRM2 domains with a Kd of 89 µM for TDP-43102-269. By binding to these RNA recognition motifs, rTRD01 partially disrupts TDP-43's interaction with the hexanucleotide RNA repeat of the disease-linked c9orf72 gene. This disruption provides a basis for studying RNA-binding dysregulation mechanisms in neurodegenerative diseases. |
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| ln Vitro |
In vitro studies have demonstrated that rTRD01 binds to TDP-43's RRM1 and RRM2 domains with a Kd of 89 µM for TDP-43102-269. The compound partially disrupts TDP-43's interaction with the hexanucleotide RNA repeat of the disease-linked c9orf72 gene. These in vitro findings support its potential for use in neurodegenerative disease research. The compound's binding to TDP-43 provides a tool for studying the role of TDP-43 in RNA metabolism and neurodegeneration.
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| ln Vivo |
In vivo studies of rTRD01 are limited as the compound is primarily used as a research tool for in vitro studies. Its ability to bind TDP-43 and disrupt RNA interactions suggests potential for in vivo evaluation in animal models of neurodegenerative diseases such as ALS and FTD. However, comprehensive in vivo pharmacological studies specifically targeting rTRD01 are not well documented in the available literature. The compound is intended for research use only and is not for human therapeutic use.
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| Enzyme Assay |
In vitro binding assays for rTRD01 typically involve testing its binding affinity to TDP-43. Binding affinity is measured using surface plasmon resonance, isothermal titration calorimetry, or fluorescence polarization assays. The compound has a Kd of 89 µM for TDP-43102-269. The compound's ability to disrupt TDP-43's interaction with RNA is assessed using electrophoretic mobility shift assays or RNA immunoprecipitation. The compound's purity and identity are assessed using analytical chemistry methods such as nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, and mass spectrometry. All assays are performed with appropriate controls.
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| Cell Assay |
In vitro cell-based assays for rTRD01 involve culturing neuronal cells to evaluate its effects on TDP-43 function and RNA binding. Cells are treated with varying concentrations of the compound and TDP-43-RNA interactions are assessed. TDP-43 localization and aggregation are monitored using immunofluorescence microscopy. Cell viability is assessed using MTT or similar colorimetric assays. The compound's effects on RNA metabolism and gene expression are evaluated by quantitative PCR or RNA sequencing. All experiments are performed in triplicate with appropriate controls to ensure statistical reliability.
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| Animal Protocol |
In vivo animal experiments for rTRD01 would be conducted to evaluate its potential in neurodegenerative disease research. Animal models of ALS or FTD would be used. Animals would be administered the compound and neurological function assessed. Parameters assessed would include motor function, survival, TDP-43 pathology, and neurodegeneration markers. Control groups receiving vehicle alone would be included for comparison. All procedures would comply with institutional animal care and use committee guidelines. Comprehensive in vivo studies are not well documented in the available literature.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of rTRD01 reflect its nature as a small molecule TDP-43 ligand. It has a molecular weight of 344.38 and the molecular formula C18H21FN4O2. The compound is soluble in DMSO and has a purity of 98% by HPLC. As a small molecule, it can cross biological membranes, including potentially the blood-brain barrier. The compound is expected to be metabolized through standard xenobiotic pathways in the liver. Complete pharmacokinetic profiling including half-life, clearance, volume of distribution, and bioavailability would require further systematic studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of rTRD01 has been evaluated in the context of its use as a research chemical. As a TDP-43 ligand, it may have biological effects that should be carefully evaluated. Proper handling procedures including use of personal protective equipment are recommended when working with pure compound. The compound is not approved for human therapeutic use and is intended for research purposes only. Long-term toxicity studies would be needed to fully establish its safety profile for pharmaceutical applications.
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| References |
[1]. François-Moutal L, et al. Small Molecule Targeting TDP-43's RNA Recognition Motifs Reduces Locomotor Defects in a Drosophila Model of Amyotrophic Lateral Sclerosis (ALS). ACS Chem Biol. 2019 Sep 20;14(9):2006-2013.
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| Additional Infomation |
6-(3-(4-Fluorobenzyl)-3-(hydroxymethyl)piperidin-1-yl)pyrazine-2-carboxamide is an organic molecular entity.
rTRD01 (CAS# 1332175-56-0) is a small molecule TDP-43 ligand with the molecular formula C18H21FN4O2 and a molecular weight of 344.38. Also known as 6-[3-(4-fluorobenzyl)-3-(hydroxymethyl)piperidin-1-yl]pyrazine-2-carboxamide, it binds to TDP-43's RRM1 and RRM2 domains with a Kd of 89 µM for TDP-43102-269. rTRD01 partially disrupts TDP-43's interaction with the hexanucleotide RNA repeat of the c9orf72 gene. It holds potential for use in neurodegenerative disease research. The compound has a purity of 98% by HPLC and is soluble in DMSO. It is intended for research use only. |
| Molecular Formula |
C18H21FN4O2
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|---|---|
| Molecular Weight |
344.38
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| Exact Mass |
344.164
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| CAS # |
1332175-56-0
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| PubChem CID |
56739767
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.292±0.06 g/cm3
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| Boiling Point |
559.7±50.0 °C
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
458
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(N)=O)=NC(N2CCCC(CC3=CC=C(F)C=C3)(CO)C2)=CN=C1
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| InChi Key |
MCTLSQYQBQKNRU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21FN4O2/c19-14-4-2-13(3-5-14)8-18(12-24)6-1-7-23(11-18)16-10-21-9-15(22-16)17(20)25/h2-5,9-10,24H,1,6-8,11-12H2,(H2,20,25)
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| Chemical Name |
6-[3-[(4-fluorophenyl)methyl]-3-(hydroxymethyl)piperidin-1-yl]pyrazine-2-carboxamide
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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) |
DMSO: 250 mg/mL (725.94 mM)
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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 | 2.9038 mL | 14.5188 mL | 29.0377 mL | |
| 5 mM | 0.5808 mL | 2.9038 mL | 5.8075 mL | |
| 10 mM | 0.2904 mL | 1.4519 mL | 2.9038 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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