| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
TDP-43 degrader-1 targets TDP-43 (TAR DNA-binding protein 43), a nuclear protein that normally functions in RNA processing and splicing. In neurodegenerative diseases such as ALS and frontotemporal dementia, TDP-43 forms cytoplasmic aggregates and undergoes pathological mislocalization. This compound promotes clearance of TDP-43 aggregates and restores its normal nuclear localization.
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| ln Vitro |
TDP-43 degrader-1 shows in vitro activity by reducing TDP-43 aggregation in cell models. It reduces the number of TDP-43-positive HuR stress granules and promotes the relocalization of abnormally distributed cytoplasmic TDP-43 back to the nucleus. This activity is beneficial for restoring normal TDP-43 function and reducing the toxicity associated with TDP-43 proteinopathy.
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| ln Vivo |
TDP-43 degrader-1 has potential in vivo activity in animal models of TDP-43 proteinopathy. By reducing TDP-43 aggregation and promoting its nuclear relocalization, the compound may ameliorate the neurodegenerative pathology associated with ALS and Alzheimer's disease. However, detailed in vivo efficacy data have not been extensively reported in the available literature.
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| Enzyme Assay |
Non-cell-based assays for TDP-43 degrader-1 may involve biochemical analysis of TDP-43 aggregation using methods such as filter trap assays or sedimentation assays. A typical protocol includes: incubating recombinant TDP-43 protein or cell lysates with the compound at various concentrations, separating aggregated and soluble TDP-43 by centrifugation or filtration, and detecting TDP-43 levels by Western blot or ELISA.
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| Cell Assay |
Cellular assays with TDP-43 degrader-1 typically involve TDP-43-overexpressing or stress-induced cell models. A representative protocol includes: culturing cells (e.g., SH-SY5Y or HeLa cells) expressing TDP-43 or treated with stress inducers, treating with TDP-43 degrader-1 at various concentrations for 24–72 hours, assessing TDP-43 aggregation by immunofluorescence microscopy, evaluating nuclear vs. cytoplasmic distribution by cell fractionation and Western blot, and measuring cell viability.
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| Animal Protocol |
In vivo animal studies with TDP-43 degrader-1 typically involve transgenic mouse models of TDP-43 proteinopathy. A representative protocol includes: administering the compound via oral gavage or intraperitoneal injection at doses determined from pharmacokinetic studies (e.g., 10–50 mg/kg daily) for several weeks, assessing TDP-43 pathology by immunohistochemistry, evaluating motor function and cognitive performance, and measuring survival in disease models.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of TDP-43 degrader-1 have not been extensively reported. As a small molecule with a molecular weight of 455.55 g/mol, it is expected to have moderate oral bioavailability and blood-brain barrier penetration (critical for CNS targets). Further PK studies are needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
Toxicological data for TDP-43 degrader-1 are limited as the compound is in preclinical research stages. Standard safety assessments would include cytotoxicity screening, hERG channel inhibition testing, and preliminary toxicology studies in animal models. As a research compound, it is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
TDP-43 degrader-1 (CAS 2902692-25-3) represents a promising approach for treating TDP-43 proteinopathies, including ALS and frontotemporal dementia. By promoting clearance of pathological TDP-43 aggregates and restoring normal nuclear localization, this compound addresses the underlying proteinopathy rather than just symptomatic relief. It is a valuable tool for studying TDP-43 biology and developing therapies for neurodegenerative diseases.
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| Exact Mass |
455.221
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|---|---|
| CAS # |
2902692-25-3
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| PubChem CID |
167346038
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
669
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=C(C2=C1N=CC(=C2)OC)/C=C/C3C4=CC(=C(C=C4CCN3)OCC5=CC=CC=C5)OC
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| InChi Key |
RKKQXGNMFVKLDL-MDZDMXLPSA-N
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| InChi Code |
InChI=1S/C28H29N3O3/c1-31-17-21(24-14-22(32-2)16-30-28(24)31)9-10-25-23-15-26(33-3)27(13-20(23)11-12-29-25)34-18-19-7-5-4-6-8-19/h4-10,13-17,25,29H,11-12,18H2,1-3H3/b10-9+
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| Chemical Name |
7-methoxy-1-[(E)-2-(5-methoxy-1-methylpyrrolo[2,3-b]pyridin-3-yl)ethenyl]-6-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (12.5 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 1.25 mg/mL (2.74 mM) (saturation unknown) in 10% DMSO + 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 DMSO stock solution (12.5 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 1.25 mg/mL (2.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (12.5 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
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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