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| Targets |
UK-101 targets the immunoproteasome β1i subunit (LMP2), which is a catalytic subunit of the immunoproteasome. The immunoproteasome is a proteolytic complex that degrades ubiquitinated proteins and generates peptides for MHC class I presentation. LMP2 (β1i) has chymotrypsin-like, trypsin-like, and caspase-like activities, and its inhibition disrupts protein degradation in immune cells and cancer cells. UK-101 is highly selective for LMP2 over the constitutive proteasome subunits β1c and β5. This selectivity makes it a valuable tool for studying the specific roles of the immunoproteasome in health and disease.
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| ln Vitro |
In a 24-hour period, PTUPB (1–10 μM) demonstrated 83% and 44% inhibitory efficacy at 10 μM and 1 μM, respectively, against human 5-LOX [1]. After three days of treatment, PTUPB (10-20) substantially reduces the proliferation of HUVECs while having negligible effects on a range of blue lineages, including as human melanoma cells and transformed endothelial cells [1]. Under various conditions, μM; 72 hours) causes cell cycle induction in the G0/1 phase. PTUPB's cell number percentages were 65.15%, 66.87%, and 65.91% at 10 μM, 15 μM, and 20 μM, respectively[1].
UK-101 exhibits potent in vitro activity as an immunoproteasome LMP2 inhibitor. It inhibits LMP2 with an IC50 of 104 nM. The compound is 144-fold more selective for LMP2 than β1c (IC50 = 15 µM) and 10-fold more selective than β5 (IC50 = 1 µM). In cell-based assays, UK-101 induces apoptosis in cancer cells, including prostate cancer cells. It causes accumulation of ubiquitinated proteins, a hallmark of proteasome inhibition. These in vitro activities confirm its utility as a research tool for studying the immunoproteasome and its role in cancer and immune function. |
| ln Vivo |
Tumor volume was decreased by UK-101 (intraperitoneal injection; 1-3 mg/kg; twice weekly; 3 weeks) in a dose-dependent manner, with the 3 mg/kg dose showing a notable reduction in tumor volume. Furthermore, mice administered UK-101 showed less systemic toxicity and maintained a steady body weight over the course of the three-week treatment period [2].
In vivo activity of UK-101 has been evaluated in animal models of cancer. In prostate cancer xenograft models, UK-101 has shown efficacy in inhibiting tumor growth. The compound induces apoptosis and inhibits cell proliferation in tumors. Its selectivity for LMP2 over constitutive proteasome subunits may reduce off-target toxicity compared to non-selective proteasome inhibitors. These in vivo studies support the potential of UK-101 as a therapeutic agent for prostate cancer and other immunoproteasome-driven diseases. |
| Enzyme Assay |
In vitro enzyme assays for UK-101 involve measuring its inhibition of immunoproteasome catalytic activity. These assays use fluorogenic substrates specific for each catalytic subunit. The enzyme is incubated with the substrate and varying concentrations of UK-101. The decrease in fluorescence is measured to determine the IC50 for each subunit (104 nM for LMP2, 15 µM for β1c, 1 µM for β5). These assays confirm the compound’s selectivity for LMP2 over other proteasome subunits.
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| Cell Assay |
Cell cycle analysis[1]
Cell Types: PC-3 cells Tested Concentrations: 2 μM; 8 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced G1 cell cycle arrest in PC-3 cells. Apoptosis analysis [1] Cell Types: PC-3 Cell Tested Concentrations: 2 μM; 8 μM Incubation Duration: 24 hrs (hours) Experimental Results: Increased apoptosis in a dose-dependent manner. Western Blot Analysis[1] Cell Types: PC-3 Cell Tested Concentrations: 1 μM; 2μM; 8 μM Incubation Duration: 24 hrs (hours) Experimental Results: PARP cleavage and p27 accumulation increased in a dose-dependent manner. In vitro cellular assays for UK-101 are conducted in cancer cell lines, particularly prostate cancer cells (e.g., LNCaP, PC-3). Cells are treated with UK-101 at various concentrations, and cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is assessed by Annexin V staining, caspase activity assays, or PARP cleavage. Accumulation of ubiquitinated proteins is measured by Western blot. These assays confirm the compound’s anti-cancer activity and its mechanism as an immunoproteasome inhibitor. |
| Animal Protocol |
Animal/Disease Models: 6weeks old male BALB/c athymic nude mice were subcutaneously (sc) (sc) implanted with PC-3 cells [2].
Doses: 1 mg/kg; 3 mg/kg. Route of Administration: intraperitoneal (ip) injection; twice a week; 3-week results. Experimental Results: Inhibits tumor growth in a mouse xenograft model of prostate cancer. In vivo animal experiments with UK-101 are conducted in mouse xenograft models of prostate cancer. Immunodeficient mice are engrafted with prostate cancer cells. UK-101 is administered via intraperitoneal injection at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of apoptosis, proteasome inhibition, and protein ubiquitination. These studies evaluate the compound’s efficacy and its mechanism of action in vivo. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for UK-101 are limited. The compound has a molecular weight of 484.74 and is lipophilic. Its bioavailability and half-life have not been extensively characterized. The compound is typically administered intraperitoneally in animal studies. Its formulation and solubility in aqueous vehicles are important for in vivo studies. Further PK studies would be needed to support any potential clinical development.
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| Toxicity/Toxicokinetics |
UK-101 is generally well-tolerated in animal studies at therapeutic doses. Its selectivity for LMP2 over constitutive proteasome subunits may reduce the toxicity associated with non-selective proteasome inhibitors. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
UK-101 is a potent and selective inhibitor of the immunoproteasome β1i (LMP2). It is also known as an LMP2 inhibitor. The compound has an IC50 of 104 nM for LMP2 and is 144-fold and 10-fold selective over β1c and β5 subunits, respectively. UK-101 induces apoptosis and is used in studies of prostate cancer and other diseases where the immunoproteasome plays a role. It is available in high purity for research applications. Its selectivity makes it a valuable tool for dissecting the roles of the immunoproteasome.
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| Molecular Formula |
C₂₅H₄₈N₂O₅SI
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| Molecular Weight |
484.74
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| Exact Mass |
484.333
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| CAS # |
1000313-40-5
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| PubChem CID |
24752894
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| Appearance |
White to off-white solid powder
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| LogP |
5.134
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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 |
16
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| Heavy Atom Count |
33
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| Complexity |
674
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CCCCCCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(CO1)CO[Si](C)(C)C(C)(C)C
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| InChi Key |
OHYPIFPQEYUPDQ-RLSLOFABSA-N
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| InChi Code |
InChI=1S/C25H48N2O5Si/c1-10-11-12-13-14-21(28)26-19(4)23(30)27-20(15-18(2)3)22(29)25(16-31-25)17-32-33(8,9)24(5,6)7/h18-20H,10-17H2,1-9H3,(H,26,28)(H,27,30)/t19-,20-,25-/m0/s1
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| Chemical Name |
N-[(2S)-1-[[(2S)-1-[(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]oxiran-2-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]heptanamide
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| Synonyms |
UK101; UK 101
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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 | 2.0630 mL | 10.3148 mL | 20.6296 mL | |
| 5 mM | 0.4126 mL | 2.0630 mL | 4.1259 mL | |
| 10 mM | 0.2063 mL | 1.0315 mL | 2.0630 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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