UK-101 is a potent and specific inhibitor of immunoproteasome β1i (LMP2) (IC50=104 nM). UK-101 is 144-fold and 10-fold more selective for LMP2 than the β1c (IC50=15 μM) and β5 (IC50=1 μM) subunits. UK-101 can cause apoptosis and may be utilized in prostate cancer-related research.

Physicochemical Properties

Molecular Formula	C₂₅H₄₈N₂O₅SI
Molecular Weight	484.74
Exact Mass	484.333
CAS #	1000313-40-5
PubChem CID	24752894
Appearance	White to off-white solid powder
LogP	5.134
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	16
Heavy Atom Count	33
Complexity	674
Defined Atom Stereocenter Count	3
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
InChi Key	OHYPIFPQEYUPDQ-RLSLOFABSA-N
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
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
Synonyms	UK101; UK 101
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)

Biological Activity

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].
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].
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.
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.
References	[1]. Structure-based design of β1i or β5i specific inhibitors of human immunoproteasomes. J Med Chem. 2014 Jul 24;57(14):6197-209. [2]. A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice. Br J Cancer. 2012 Jun 26;107(1):53-62.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.