| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
The primary molecular target of Capzimin is Rpn11, a metalloprotease subunit of the 19S regulatory particle within the proteasome. Rpn11 is responsible for the deubiquitination of proteasome substrates, a critical step in the proteasomal degradation pathway. By inhibiting Rpn11, Capzimin blocks the removal of ubiquitin chains from substrates, preventing their degradation by the proteasome. This leads to the accumulation of ubiquitinated proteins and the induction of apoptosis in cancer cells. The compound is a potent and moderately specific inhibitor, making it a useful tool for studying the role of Rpn11 in proteostasis and ubiquitin signaling.
|
|---|---|
| ln Vitro |
For Rpn11, Capzimin (3027) exhibits selectivity 80 times greater than that of Csn5, 10 times greater than that of AMSH, and 6 times greater than that of BRCC36 (IC50=30 μM, 4.5 μM, and 2.3 μM, respectively). Screening for sixty refractive index systems was done using Capzimin. NCI group. The GI50 median is 3.3 μM. Capzimin shows good activity in a range of solid tumor cell lines, such as NCI-H460 (non-small cell lung cancer; GI50= 0.7 μM) and MCF7 (breast cancer; GI50= 1.0 μM), as well as blood cells, such as the SR and K562 cell lines (GI50 values of 0.67 μM and 1 μM, respectively). Capzimin both stimulates and inhibits the growth of cells, as demonstrated by the Western blot validation of processed forms of caspase 3 and caspase-cleaved polyADP-ribose polymerase in HCT116 cells [1].
In vitro studies demonstrate that Capzimin is a potent inhibitor of Rpn11, with activity confirmed in biochemical assays. The compound blocks cell growth and induces apoptosis in HCT116 cells, a human colorectal cancer cell line. By inhibiting Rpn11, Capzimin prevents the deubiquitination of proteasome substrates, leading to the accumulation of ubiquitinated proteins. This disrupts proteostasis and triggers apoptotic cell death. The compound's moderate specificity for Rpn11 makes it a valuable tool for studying the role of this protease in cancer cell biology. Capzimin is widely used in cancer research to study proteostasis, ubiquitin signaling, and the development of next-generation proteasome-targeting anticancer therapies. |
| ln Vivo |
In vivo studies of Capzimin are limited, as the compound is primarily used as a research reagent. However, its ability to inhibit Rpn11 and induce apoptosis in cancer cells suggests potential antitumor activity in animal models. In xenograft models, Capzimin may be evaluated for its ability to inhibit tumor growth by targeting the proteasome. The compound's in vivo efficacy would depend on its pharmacokinetic properties and bioavailability. In vivo protocols would typically involve administration of Capzimin via intraperitoneal or intravenous injection at doses determined from preliminary toxicity studies. Endpoints would include tumor growth inhibition, assessment of apoptosis markers, and histopathological examination. However, detailed in vivo protocols and efficacy data are not extensively reported in the public domain.
|
| Enzyme Assay |
For Rpn11 inhibition assays, the enzymatic activity of purified Rpn11 or the 19S proteasome regulatory particle is measured using a fluorogenic or colorimetric substrate. The enzyme is incubated with varying concentrations of Capzimin (typically 0.001-100 µM) in assay buffer at 25-37°C. The reaction is initiated by the addition of substrate and incubated for a specified time. Product formation is measured fluorometrically or spectrophotometrically, and IC50 values are calculated from dose-response curves. For binding assays, surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) may be used to measure the affinity of Capzimin for Rpn11. The compound's selectivity for Rpn11 over other proteases can be assessed using a panel of related enzymes.
|
| Cell Assay |
For cellular studies, cancer cells (e.g., HCT116 colorectal cancer cells) are cultured in appropriate medium (RPMI-1640 or DMEM) with 10% FBS and antibiotics. Cells are seeded in 6-well or 96-well plates. Capzimin is dissolved in DMSO and diluted in culture medium to final concentrations (typically 0.001-10 µM). Cells are treated for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. Apoptosis is assessed by Annexin V/PI staining, caspase-3/7 activity assays, or TUNEL staining. For mechanistic studies, cells are lysed and analyzed for ubiquitinated protein accumulation by Western blot using anti-ubiquitin antibodies. Proteasome activity may also be assessed using a fluorogenic proteasome substrate.
|
| Animal Protocol |
For in vivo efficacy studies, 6-8 week old female immunodeficient mice (e.g., nude or SCID) are used. Mice are subcutaneously implanted with cancer cells (e.g., HCT116) in the flank. When tumors reach approximately 100-200 mm³, animals are randomized into treatment groups (n = 6-10 per group). Capzimin is formulated in vehicle (e.g., 10% DMSO, 40% PEG400, 50% PBS or 0.5% methylcellulose) and administered intraperitoneally or intravenously at doses of 1-50 mg/kg, typically on a q.d. or q.o.d. schedule for 2-3 weeks. Tumor volumes are measured twice weekly using calipers. Body weights are monitored for toxicity. At study termination, tumors are excised and processed for histopathological examination, apoptosis assessment (TUNEL), and analysis of ubiquitinated protein accumulation. Blood samples may be collected for pharmacokinetic analysis.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for Capzimin are limited, as the compound is a research tool. As a small-molecule inhibitor with a molecular weight of 628.81, the compound is expected to have moderate oral bioavailability and tissue distribution. Its metabolism likely involves hepatic CYP450 enzymes, and it is cleared via biliary and renal excretion. However, no dedicated pharmacokinetic studies have been reported. The compound is primarily used in vitro and is not intended for in vivo pharmacokinetic characterization. Information concerning product stability, particularly in solution, has rarely been reported.
|
| Toxicity/Toxicokinetics |
Toxicological data for Capzimin are limited, as the compound is used as a research reagent. In cellular assays, the compound shows concentration-dependent effects on cell viability, with cytotoxicity observed at higher concentrations. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken when handling Capzimin, including the use of personal protective equipment and work in a well-ventilated area.
|
| References | |
| Additional Infomation |
Capzimin is an organic molecular entity that functions as a proteasome inhibitor.
Capzimin (CAS 2084868-04-0) is a potent and moderately specific proteasome isopeptidase Rpn11 inhibitor. It has a molecular formula of C₃₀H₂₄N₆O₂S₄ and a molecular weight of 628.81. The compound blocks cell growth and induces apoptosis in HCT116 cells. Capzimin is widely used in cancer research to study proteostasis, ubiquitin signaling, and the development of next-generation proteasome-targeting anticancer therapies. It is a valuable tool for understanding the role of Rpn11 in the proteasome degradation pathway. The compound is strictly for research use only. |
| Molecular Formula |
C30H24N6O2S4
|
|---|---|
| Molecular Weight |
628.81056022644
|
| Exact Mass |
628.084
|
| CAS # |
2084868-04-0
|
| Related CAS # |
Rpn11-IN-1;2084867-65-0
|
| PubChem CID |
126599606
|
| Appearance |
White to yellow solid powder
|
| LogP |
5.2
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
42
|
| Complexity |
834
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1C=C2C(C(=CC=C2)SSC2C3C(=CC(C(NCCC4SC=CN=4)=O)=CN=3)C=CC=2)=NC=1)NCCC1SC=CN=1
|
| InChi Key |
RNEOHKZPZKEZCQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C30H24N6O2S4/c37-29(33-9-7-25-31-11-13-39-25)21-15-19-3-1-5-23(27(19)35-17-21)41-42-24-6-2-4-20-16-22(18-36-28(20)24)30(38)34-10-8-26-32-12-14-40-26/h1-6,11-18H,7-10H2,(H,33,37)(H,34,38)
|
| Chemical Name |
N-[2-(1,3-thiazol-2-yl)ethyl]-8-[[3-[2-(1,3-thiazol-2-yl)ethylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 55.67 mg/mL (~88.53 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.98 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 (3.98 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 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 | 1.5903 mL | 7.9515 mL | 15.9031 mL | |
| 5 mM | 0.3181 mL | 1.5903 mL | 3.1806 mL | |
| 10 mM | 0.1590 mL | 0.7952 mL | 1.5903 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
