| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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Purity: ≥98%
| Targets |
Rpn11 (also known as PSMD14), a proteasome-associated deubiquitinase that is a key component of the 19S regulatory particle of the 26S proteasome. Rpn11 is a Zn2+-dependent metalloisopeptidase that hydrolyzes ubiquitin from tagged proteins that are trafficked to the proteasome for degradation. Capzimin is a potent and moderately specific proteasome isopeptidase Rpn11 inhibitor with an IC50 of 390 nM. The compound shows 80-fold selectivity for Rpn11 over Csn5, ten-fold over AMSH, and six-fold over BRCC36.
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| ln Vitro |
Capzimin inhibits Rpn11, blocking the removal of polyubiquitin chains from substrates destined for proteasomal degradation. This inhibition disrupts proteasomal degradation of ubiquitinated proteins, leading to accumulation of polyubiquitinated proteins and induction of cellular stress. In leukemia cells, Capzimin exhibits GI50s of 0.67 μM and 1 μM in SR and K562 cell lines. The compound both stimulates and inhibits the growth of cells, as demonstrated by Western blot validation of processed forms of caspase 3 and caspase-cleaved PARP in HCT116 cells.
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| ln Vivo |
Zn2+-dependent metalloisopeptidase Rpn11 hydrolyzes ubiquitin in proteins that have been tagged, sending the proteins to the proteasome for destruction. There was a notable decrease in Rpn11-inhibition activity when Rpn11-IN-1 (compound 35) was tested in the presence of Zn(cyclen)2+ (100 μM) (IC50=77.4 μM vs. 0.39 μM). Zn(cyclen)2+'s capacity to compete with or titrate Rpn11-IN-1 away from Rpn11 is thought to be the cause of the observed shifts in IC50 values. Rpn11-IN-1 inhibits the growth of tumor cells in vitro. Rpn11-IN-1's IC50 values on A549 and 293T cells are 3.8 μM and 2.1 μM, respectively[1].
In vivo, capzimin has been evaluated in preclinical cancer models. The compound blocks the proliferation of tumor cells in culture. Capzimin was screened against the NCI panel of 60 cancer cell lines. The compound's ability to inhibit Rpn11 and disrupt proteasomal degradation makes it a promising candidate for cancer therapy, particularly in cancers that are dependent on proteasome function for survival. However, detailed in vivo efficacy data in animal models is limited. |
| Enzyme Assay |
In vitro enzyme assays for capzimin involve measuring the inhibition of Rpn11 deubiquitinase activity using fluorogenic ubiquitin-AMC (7-amino-4-methylcoumarin) substrates. The enzyme is incubated with substrate and various concentrations of capzimin, and the release of fluorescent AMC is monitored over time. IC50 values are determined from concentration-response curves. Capzimin shows an IC50 of 390 nM for Rpn11 inhibition.
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| Cell Assay |
Cellular assays for capzimin involve treating cancer cell lines (such as leukemia cells SR and K562, or HCT116 colon cancer cells) with the compound and measuring cell proliferation, apoptosis, and accumulation of polyubiquitinated proteins. Cell viability is assessed by MTT or other metabolic assays. Apoptosis is measured by Western blot for cleaved caspase 3 and PARP. Capzimin exhibits GI50s of 0.67 μM and 1 μM in SR and K562 cell lines, and induces apoptosis in HCT116 cells.
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| Animal Protocol |
In vivo animal studies for capzimin are limited, as the compound is primarily used as a research tool. Studies in xenograft models of cancer would involve administration of capzimin to tumor-bearing mice and measurement of tumor growth inhibition. Pharmacokinetic parameters would be determined from serial blood sampling. Further studies are needed to fully characterize the in vivo efficacy of capzimin.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for capzimin is limited and primarily derived from research use. The compound's properties as a small molecule suggest it may have reasonable oral bioavailability and tissue distribution. However, detailed pharmacokinetic studies are needed to support further development. The compound is primarily used as a chemical probe for research purposes.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of capzimin are limited. As a proteasome inhibitor, capzimin has the potential to cause toxicity related to its mechanism of action, including disruption of protein homeostasis and induction of cellular stress. The compound's selectivity for Rpn11 over other deubiquitinases (80-fold over Csn5, ten-fold over AMSH, six-fold over BRCC36) may contribute to a more favorable toxicity profile compared to less selective proteasome inhibitors.
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| References |
[1]. Perez C, et al. Discovery of an Inhibitor of the Proteasome Subunit Rpn11. J Med Chem. 2017 Feb 23;60(4):1343-1361
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| Additional Infomation |
Capzimin is a first-in-class, potent, and specific inhibitor of the proteasome-associated deubiquitinase Rpn11 (PSMD14). It is widely used in cancer research to study proteostasis, ubiquitin signaling, and the development of next-generation proteasome-targeting anticancer therapies. The compound shows 80-fold selectivity for Rpn11 over Csn5, ten-fold over AMSH, and six-fold over BRCC36. Capzimin is a valuable chemical probe for investigating the role of Rpn11 in proteasomal degradation and its potential as a therapeutic target in cancer.
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| Molecular Formula |
C15H13N3OS2
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|---|---|
| Molecular Weight |
315.41322016716
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| Exact Mass |
315.05
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| CAS # |
2084867-65-0
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| Related CAS # |
Capzimin;2084868-04-0
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| PubChem CID |
124081114
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| Appearance |
White to yellow solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
369
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C=CN=C1CCNC(C1=CN=C2C(=CC=CC2=C1)S)=O
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| InChi Key |
MYNGHZGMRXNEEH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13N3OS2/c19-15(17-5-4-13-16-6-7-21-13)11-8-10-2-1-3-12(20)14(10)18-9-11/h1-3,6-9,20H,4-5H2,(H,17,19)
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| Chemical Name |
8-sulfanyl-N-[2-(1,3-thiazol-2-yl)ethyl]quinoline-3-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.1705 mL | 15.8524 mL | 31.7048 mL | |
| 5 mM | 0.6341 mL | 3.1705 mL | 6.3410 mL | |
| 10 mM | 0.3170 mL | 1.5852 mL | 3.1705 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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