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| Targets |
Ubiquitin-specific peptidase 30 (USP30). USP30 inhibitor 11 is a potent and selective inhibitor of USP30 with an IC50 of 0.01 µM. USP30 is a deubiquitinating enzyme that localizes to the outer mitochondrial membrane and removes ubiquitin chains from mitochondrial proteins, counteracting the Parkin-mediated ubiquitination that marks mitochondria for mitophagy. By inhibiting USP30, USP30 inhibitor 11 promotes the accumulation of ubiquitinated mitochondrial proteins, enhancing mitophagy and mitochondrial quality control. USP30 has been implicated in cancer and neurodegenerative diseases, including Parkinson's disease, making it a therapeutic target of interest.
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| ln Vitro |
USP30 is a 517-amino acid protein that is present in the outer membrane of the mitochondria. It has been demonstrated to deubiquitinate a large number of mitochondrial proteins and is the only deubiquitinating enzyme with a mitochondrial addressing signal [1]. In the USP30 biochemical IC50 assay, USP30 Inhibitor 11 (0.01-30 µM; λEx=540 nm; λEm=590 nm) suppresses USP30 biochemical activity with an IC50 of 0.01 µM [1].
USP30 inhibitor 11 demonstrates potent in vitro activity against USP30 with an IC50 of 0.01 µM. In cell-based assays, USP30 inhibition by this compound leads to increased ubiquitination of mitochondrial proteins and enhanced mitophagy. The compound's selectivity for USP30 over other deubiquitinating enzymes has been confirmed in selectivity profiling studies. USP30 inhibitor 11 is used to study the role of USP30 in cancer and mitochondrial dysfunction. Further detailed in vitro data, including selectivity profiles and cellular effects, are available in the primary literature and patent WO2017009650A1. |
| ln Vivo |
In vivo activity of USP30 inhibitor 11 has been investigated in preclinical models of cancer and mitochondrial dysfunction. By inhibiting USP30, the compound promotes mitophagy and may have therapeutic effects in diseases where mitochondrial dysfunction plays a role, such as cancer and Parkinson's disease. However, specific in vivo data, including efficacy in animal models, pharmacokinetics, and toxicity, are not extensively detailed in the available literature summary. Further information would be available in the primary research publications.
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| Enzyme Assay |
Enzyme inhibition assays for USP30 inhibitor 11 are performed using recombinant USP30 enzyme. The compound is incubated with the enzyme and a ubiquitin-AMC (7-amino-4-methylcoumarin) substrate, and the inhibition of deubiquitinating activity is measured by monitoring the increase in fluorescence upon substrate cleavage. The IC50 value of 0.01 µM is determined from dose-response curves. Selectivity against other deubiquitinating enzymes is assessed using similar assays with recombinant enzymes.
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| Cell Assay |
Cell-based assays for USP30 inhibitor 11 are conducted using cell lines to study mitophagy and mitochondrial quality control. Cells are treated with the compound at various concentrations, and the following endpoints are assessed: ubiquitination of mitochondrial proteins (by Western blot or immunoprecipitation), mitophagy (by mitochondrial marker degradation or by using mitophagy reporter systems), mitochondrial function (by oxygen consumption rate or membrane potential measurements), and cell viability. The specificity of the observed effects can be confirmed by using cells with USP30 knockdown or by using other USP30 inhibitors as comparators.
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| Animal Protocol |
In vivo studies for USP30 inhibitor 11 would typically involve administration to animal models of cancer or mitochondrial dysfunction. The compound's ability to inhibit USP30 activity in tissues can be assessed by measuring ubiquitination of mitochondrial proteins. However, specific in vivo data for USP30 inhibitor 11 are not extensively detailed in the available literature summary.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of USP30 inhibitor 11 are not extensively reported in the available literature. As a small molecule USP30 inhibitor with a molecular weight of 368.41, the compound would be expected to have reasonable bioavailability if administered appropriately, though this would need to be confirmed experimentally. Storage recommendations include -20°C for long-term storage. The compound is soluble in DMSO and other organic solvents.
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| Toxicity/Toxicokinetics |
Toxicological data for USP30 inhibitor 11 are not extensively reported in the available literature. The compound is intended for research use only and is not approved for clinical use. Standard laboratory safety precautions should be followed when handling the compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety glasses) and proper ventilation.
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| References | |
| Additional Infomation |
USP30 inhibitor 11 is a selective and potent USP30 inhibitor (IC50 = 0.01 µM) that is used to study cancer and conditions involving mitochondrial dysfunction. It is a valuable probe for investigating mitophagy and ubiquitin-mediated quality control. The compound is not approved for clinical use and is supplied for research purposes only. It is available from multiple chemical suppliers.
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| Molecular Formula |
C17H16N6O2S
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|---|---|
| Molecular Weight |
368.412940979004
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| Exact Mass |
368.105
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| CAS # |
2067332-64-1
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| PubChem CID |
124197552
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
627
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1(C#N)CCCC1C(N(C1=NC(C2=NC(C#N)=C(OC)C=C2)=CS1)C)=O
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| InChi Key |
APFKLZAHDDDAOH-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C17H16N6O2S/c1-22(16(24)14-4-3-7-23(14)10-19)17-21-13(9-26-17)11-5-6-15(25-2)12(8-18)20-11/h5-6,9,14H,3-4,7H2,1-2H3/t14-/m0/s1
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| Chemical Name |
(2S)-1-cyano-N-[4-(6-cyano-5-methoxypyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide
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| Synonyms |
USP30 inhibitor 11 USP30 inhibitor 11
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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 : ~33.33 mg/mL (~90.47 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 | 2.7144 mL | 13.5718 mL | 27.1437 mL | |
| 5 mM | 0.5429 mL | 2.7144 mL | 5.4287 mL | |
| 10 mM | 0.2714 mL | 1.3572 mL | 2.7144 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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