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| Targets |
PSI targets the proteasome, a multi-catalytic protease complex responsible for the degradation of ubiquitinated proteins. The proteasome plays a critical role in maintaining cellular protein homeostasis by degrading misfolded, damaged, or regulatory proteins. By inhibiting the chymotrypsin-like activity of the proteasome, PSI prevents the degradation of pro-apoptotic proteins and cell cycle regulators, leading to cell cycle arrest and apoptosis. This mechanism is the basis for the use of proteasome inhibitors in cancer therapy.
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| ln Vitro |
Primary effusion lymphoma (PEL) cells are inhibited from proliferating by PSI (24 hours) at low nanomolar concentrations (CC50 of BJAB, Ramos, BC3, and BCBL1 cells are 205, 190, 22.0, and 53.0 nM, respectively) [1]. In comparison to control, caspase-3/7 activity is increased eight-fold by PSI (50 nM; 6 hours) [1]. 52% less NF-κB transcriptional activity is seen at 50 nM PSI for 6 hours [1]. At high concentrations (5 nM), PSI (1, 5 nM; 3 days) suppresses the development of BC3 cells [1].
In vitro, PSI demonstrates potent inhibition of the chymotrypsin-like activity of the proteasome. In cell-based assays, PSI induces the accumulation of ubiquitinated proteins and causes cell cycle arrest and apoptosis in cancer cell lines. Its activity is concentration-dependent, with effective concentrations typically in the nanomolar to micromolar range. Its potent inhibition of the proteasome makes it a valuable tool for studying the ubiquitin-proteasome pathway and for developing proteasome-targeted anticancer therapies. |
| ln Vivo |
In vivo, PSI has been studied in preclinical models of cancer. Its ability to inhibit the proteasome and induce apoptosis may lead to antitumor effects. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying the ubiquitin-proteasome pathway. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
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| Enzyme Assay |
The in vitro proteasome inhibition assay for PSI typically uses purified 20S or 26S proteasome and a fluorogenic substrate for the chymotrypsin-like activity (e.g., Suc-LLVY-AMC). The assay is performed in 96-well plates with the enzyme, substrate, and varying concentrations of the test compound (typically 0.1 nM to 10 µM) at 37°C for 30-60 minutes. The release of AMC is measured fluorometrically at excitation/emission wavelengths of 360/460 nm. IC50 values are calculated from dose-response curves using nonlinear regression. Positive controls (e.g., MG132, bortezomib) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
Cytotoxicity assay [1]
Cell Types: BC3, BCBL1, Ramos, BJAB Cell Tested Concentrations: Incubation Duration: 24 h Experimental Results: Low nanomolar concentration (CC50 is 205, 190, 22.0, BJAB, Ramos, BC3, BCBL1 cells are 53.0, respectively nM). Western Blot Analysis[1] Cell Types: HBL6 Cell Tested Concentrations: 50 nM Incubation Duration: 6 hrs (hours) Experimental Results: NF-κB activity diminished by 52%. For in vitro cellular assays, cancer cell lines are treated with PSI at concentrations ranging from 0.01 to 10 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Ubiquitinated protein accumulation is assessed by Western blotting using anti-ubiquitin antibodies. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls and are performed in triplicate. |
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are subcutaneously inoculated with cancer cells. When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). PSI is administered intraperitoneally or intravenously at doses ranging from 0.1 to 10 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis of ubiquitinated proteins and immunohistochemistry. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of PSI have been partially characterized. Following intraperitoneal or intravenous administration, the compound shows rapid absorption and distribution. Plasma half-life is estimated to be 1-2 hours. The compound distributes into tissues including tumor, liver, and kidney. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of PSI are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 10 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
PSI is a potent, selective, and irreversible inhibitor of the proteasome. It inhibits the chymotrypsin-like activity of the proteasome, leading to the accumulation of ubiquitinated proteins and induction of apoptosis. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use. Its potent proteasome inhibition makes it a valuable tool for studying the ubiquitin-proteasome pathway and for developing proteasome-targeted anticancer therapies.
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| Molecular Formula |
C32H50N4O8
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| Molecular Weight |
618.7614
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| Exact Mass |
618.362
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| CAS # |
158442-41-2
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| Related CAS # |
PSI TFA
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| PubChem CID |
9960660
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
844.2±65.0 °C at 760 mmHg
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| Flash Point |
464.4±34.3 °C
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| Vapour Pressure |
0.0±3.1 mmHg at 25°C
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| Index of Refraction |
1.510
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| LogP |
5.79
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
44
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| Complexity |
958
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C=O)NC(=O)OCC1=CC=CC=C1
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| InChi Key |
TYFTWYMXUWCOOB-YICLCXKGSA-N
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| InChi Code |
InChI=1S/C32H50N4O8/c1-9-21(4)27(36-31(42)43-19-23-13-11-10-12-14-23)30(41)35-25(15-16-26(38)44-32(6,7)8)29(40)33-22(5)28(39)34-24(18-37)17-20(2)3/h10-14,18,20-22,24-25,27H,9,15-17,19H2,1-8H3,(H,33,40)(H,34,39)(H,35,41)(H,36,42)/t21-,22-,24-,25-,27-/m0/s1
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| Chemical Name |
tert-butyl (4S)-5-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate
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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, 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) |
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 | 1.6161 mL | 8.0807 mL | 16.1614 mL | |
| 5 mM | 0.3232 mL | 1.6161 mL | 3.2323 mL | |
| 10 mM | 0.1616 mL | 0.8081 mL | 1.6161 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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