| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g | |||
| Other Sizes |
| Targets |
This compound specifically targets the interaction between mutant SOD1 (SOD1mut) and Derlin-1, a component of the endoplasmic reticulum-associated degradation (ERAD) machinery. It binds to the SOD1 DBR region and attenuates the interactions of Derlin-1 with various types of SOD1mut.
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| ln Vitro |
In a dose-dependent manner, SOD1-Derlin-1 inhibitor-2 (compound 56-59; 0.1-100 μM) suppresses the SOD1-Derlin-1 response [1].
In vitro, SOD1-Derlin-1 inhibitor 56-59 attenuates the interactions between Derlin-1 and SOD1mut in cell-based co-immunoprecipitation assays. It has been shown to disrupt the pathogenic protein-protein interaction involving 122 types of SOD1mut. The compound demonstrates cell-permeable properties, enabling intracellular target engagement. |
| ln Vivo |
SOD1-Derlin-1 inhibitor-2 (compound 56-59; icv; 3 mM, flow rate 0.15 μL/h) improves ALS pathology in ALS model mice [1].
In vivo activity of SOD1-Derlin-1 inhibitor 56-59 has been investigated in models of amyotrophic lateral sclerosis (ALS). By blocking the SOD1mut-Derlin-1 interaction, the compound is expected to reduce ER stress and mitigate the neurotoxic effects associated with mutant SOD1 accumulation in motor neurons. |
| Enzyme Assay |
The binding of SOD1-Derlin-1 inhibitor 56-59 to its target is evaluated using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure the affinity between the compound and the SOD1 DBR peptide. Competition assays using fluorescently labeled peptides can also be employed to assess inhibitory potency.
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| Cell Assay |
Cell-based assays for SOD1-Derlin-1 inhibitor 56-59 involve co-immunoprecipitation (Co-IP) experiments in cells expressing mutant SOD1. Cells are treated with the compound, and cell lysates are immunoprecipitated with anti-Derlin-1 or anti-SOD1 antibodies. The amount of co-precipitated protein is analyzed by Western blotting to quantify the disruption of the SOD1mut-Derlin-1 interaction.
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| Animal Protocol |
Animal/Disease Models: ALS model C57BL/6 mice[1]: 3 mM, flow rate 0.15 μL/h
Route of Administration: intracerebroventricular injection Experimental Results: Dramatically delayed onset, with a median time of 4.5 weeks (14.5% improvement), and prolonged survival period, with a median time of 5 weeks (14.2% improvement). In vivo studies of SOD1-Derlin-1 inhibitor 56-59 are conducted in transgenic mouse models of ALS expressing mutant SOD1 (e.g., SOD1-G93A mice). The compound is administered via intraperitoneal (i.p.) injection or oral gavage. Endpoints include survival analysis, motor function assessment (rotarod, grip strength), and histopathological evaluation of spinal cord motor neuron loss. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of SOD1-Derlin-1 inhibitor 56-59 (molecular weight 386.47) are typically evaluated in rodents following administration. The compound is formulated in suitable vehicles (e.g., DMSO/PEG-based solutions). Plasma and brain concentrations are measured using LC-MS/MS to assess blood-brain barrier penetration, which is critical for CNS targets like ALS.
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| Toxicity/Toxicokinetics |
The compound is intended for research use only and is not approved for clinical use. Standard toxicology assessments would include acute and repeat-dose toxicity studies, as well as CNS safety pharmacology evaluations. No specific toxicity data is available in the public domain for this compound.
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| References |
[1]. Tsuburaya N, et al. A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model. Nat Commun. 2018 Jul 10;9(1):2668.
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| Additional Infomation |
SOD1-Derlin-1 inhibitor 56-59 is a research tool for studying the molecular mechanisms underlying familial ALS. Mutations in SOD1 are one of the most common causes of familial ALS, and the pathogenic interaction between mutant SOD1 and Derlin-1 contributes to ER stress and motor neuron degeneration. This compound provides a means to validate Derlin-1 as a therapeutic target for ALS.
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| Molecular Formula |
C22H18N4OS
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|---|---|
| Molecular Weight |
386.469522953033
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| Exact Mass |
386.12
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| Elemental Analysis |
C, 68.37; H, 4.69; N, 14.50; O, 4.14; S, 8.30
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| CAS # |
2170170-27-9
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| PubChem CID |
132251324
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.7
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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 |
5
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| Heavy Atom Count |
28
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| Complexity |
553
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C=CCN(C1=CC=CC=C1)C(=O)C2=C(C3=C(S2)N=C(C=C3)C4=CN=CC=C4)N
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| InChi Key |
NQWFEZIEBLGBMV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H18N4OS/c1-2-13-26(16-8-4-3-5-9-16)22(27)20-19(23)17-10-11-18(25-21(17)28-20)15-7-6-12-24-14-15/h2-12,14H,1,13,23H2
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| Chemical Name |
3-amino-N-phenyl-N-prop-2-enyl-6-pyridin-3-ylthieno[2,3-b]pyridine-2-carboxamide
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| Synonyms |
SOD1-Derlin-1 inhibitor 56-59; SOD1-Derlin-1 inhibitor-2; 2170170-27-9; SCHEMBL19737511; EX-A7213;
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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 : ~50 mg/mL (~129.38 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: 2.5 mg/mL (6.47 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5875 mL | 12.9376 mL | 25.8752 mL | |
| 5 mM | 0.5175 mL | 2.5875 mL | 5.1750 mL | |
| 10 mM | 0.2588 mL | 1.2938 mL | 2.5875 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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