| Size | Price | Stock | Qty |
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| Targets |
Kd: 17±7 μM (EXOSC3-RNA interaction)[1]
ERD03 targets EXOSC3 (exosome component 3), a core protein of the RNA exosome complex responsible for RNA processing and degradation. By binding specifically to EXOSC3 (Kd = 17 +/- 7 microM), ERD03 disrupts the interaction between EXOSC3 and RNA, leading to impaired RNA processing. Alternative reports indicate it may also antagonize the orexin-1 receptor (OX1R). |
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| ln Vitro |
At 50 μM, ERD03 demonstrates ~18% suppression of G-rich RNA and EXOSC3 binding[1]. In zebrafish embryos, ERD03 (50 μM; 5 days) significantly curvatures the spinal column and reproduces the PCH1B phenotype during development[1]. In embryos, ERD03 (50 μM) causes a small buildup of ataxin1a mRNA and causes a ~6-fold overexpression of ataxin1b mRNA. Zebrafish cerebella shrink to half their control brain size in DMSO as a result of ERD03-induced cerebellar atrophy[1].
In vitro, ERD03 disrupts EXOSC3-RNA interactions in a concentration-dependent manner. Binding studies show it specifically binds EXOSC3 with a Kd of 17 microM. It impairs RNA exosome function, leading to accumulation of RNA processing intermediates. This activity makes it useful for studying the molecular mechanisms underlying PCH1B and other RNA processing disorders. |
| ln Vivo |
In vivo, ERD03 induces a PCH1B-like phenotype in zebrafish embryos, including characteristic cerebellar hypoplasia and motor neuron defects. When administered to developing zebrafish (typically at 1-10 uM in the water), it recapitulates key features of the human neurological disease, making it an excellent tool for studying pathogenesis and testing potential therapeutic interventions for PCH1B.
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| Enzyme Assay |
Surface plasmon resonance (SPR) is used to measure direct binding to EXOSC3. Recombinant EXOSC3 protein is immobilized on a sensor chip. ERD03 at increasing concentrations (0-100 uM) is flowed over the chip, and the association and dissociation rates are monitored. The dissociation constant (Kd) is calculated from the binding curves, with a reported Kd of 17 +/- 7 microM for the EXOSC3-RNA disruptor activity.
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| Cell Assay |
Cellular assays measuring RNA exosome activity are used. Human cell lines (e.g., HeLa or SH-SY5Y) are treated with ERD03 (10-50 uM) for 24-48 hours. Total RNA is extracted, and the levels of specific RNA processing intermediates (e.g., 5.8S rRNA precursors or specific mRNA decay intermediates) are measured by Northern blot or qRT-PCR. Accumulation of these intermediates indicates disruption of EXOSC3-RNA interactions and impaired exosome function.
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| Animal Protocol |
The in vivo disease model uses zebrafish embryos. Wild-type zebrafish embryos at 6-24 hours post-fertilization (hpf) are placed in egg water containing ERD03 at concentrations of 1-100 uM. The embryos are incubated at 28.5degC for 48-96 hours. They are then examined under a microscope for morphological defects characteristic of PCH1B, particularly cerebellar hypoplasia and abnormal motor behavior. Whole-mount in situ hybridization can be used to assess brain morphology and neuronal marker expression.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ERD03 have not been fully published. As a small molecule with molecular weight 339.43 (C21H25NO3) and moderate lipophilicity, it is likely to have reasonable cell permeability. For zebrafish studies, it is administered in aqueous solution where it is absorbed through the skin and gills. Solubility is likely in DMSO (stock solution) and subsequent dilution in water or PBS.
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| Toxicity/Toxicokinetics |
Specific toxicity data is limited, but at concentrations used for zebrafish studies (1-10 uM), ERD03 is well-tolerated by the embryos and does not cause non-specific lethality or generalized developmental arrest. At higher concentrations (above 50 uM), it may cause non-specific toxicity or mortality. Standard laboratory safety precautions should be observed. It is not a human therapeutic and has no clinical safety data.
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| References |
[1]. Liberty François-Moutal, et al. A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B). ACS Chem Biol. 2018 Oct 19;13(10):3000-3010.
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| Additional Infomation |
(4-Hydroxy-3,4-dihydroisoquinoline-2(1H)-yl)[3-(3-hydroxy-3-methylbutyl)phenyl] ketone is an isoquinoline alcohol, specifically 1,2,3,4-Tetrahydroisoquinolines-4-ol, in which the hydrogen atom on the secondary amine is replaced by a 3-(3-hydroxy-3-methylbutyl)benzoyl group. It is a tertiary amide, tertiary alcohol, secondary alcohol, isoquinoline alcohol, and also a benzamide compound.
ERD03 is also known as EXOSC3-RNA disrupting compound 3. The compound is used for studying pontocerebellar hypoplasia type 1B (PCH1B) and other brain neurodegenerative diseases. Alternative reported activity as an orexin-1 receptor antagonist suggests it may be a dual-purpose tool, though the primary validated use is for EXOSC3 disruption. It remains a preclinical research tool. |
| Molecular Formula |
C21H25NO3
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|---|---|
| Molecular Weight |
339.43
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| Exact Mass |
339.183
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| CAS # |
1377897-01-2
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| PubChem CID |
70761166
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
464
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(CCC1=CC(=CC=C1)C(=O)N2CC(C3=CC=CC=C3C2)O)O
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| InChi Key |
HYVUFYJZMRRTOP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25NO3/c1-21(2,25)11-10-15-6-5-8-16(12-15)20(24)22-13-17-7-3-4-9-18(17)19(23)14-22/h3-9,12,19,23,25H,10-11,13-14H2,1-2H3
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| Chemical Name |
(4-hydroxy-3,4-dihydro-1H-isoquinolin-2-yl)-[3-(3-hydroxy-3-methylbutyl)phenyl]methanone
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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 (e.g. under nitrogen), 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) |
DMSO: 100 mg/mL (294.61 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 | 2.9461 mL | 14.7306 mL | 29.4612 mL | |
| 5 mM | 0.5892 mL | 2.9461 mL | 5.8922 mL | |
| 10 mM | 0.2946 mL | 1.4731 mL | 2.9461 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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