| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
EZH2
EZH2 (Enhancer of Zeste Homolog 2). |
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| ln Vitro |
NUCC-0226272 (0.01-10 μM; 5 days) has antiproliferative effects on LNCaP and 22Rv1 cells[1]. NUCC-0226272 (10 μM; 6 days) showed strong degradation of EZH2, reduction of the PRC2 component SUZ12, and decreased H3K27me3 levels in C4-2B cells[1].
In biochemical assays, NUCC-0226272 induces potent degradation of EZH2 protein. The compound exhibits significant anti‑proliferative effects in cancer cells that depend on EZH2 activity. The molecular formula is C₆₇H₉1N₉O₈S and the molecular weight is 1182.56. |
| ln Vivo |
Pharmacokinetic Parameters of NUCC-0226272 in C57Bl/6 mouse[1]. IP (4 mg/kg) Tmax (h) 0.83 Cmax (ng/mL) 3650 AUClast (min·ng/mL) 12777389 t1/2 (h) 3.46 CL (mL/min/kg) 3.11 Vss (L/kg) 3.11
This entry is not available. As an EZH2 degrader, NUCC-0226272 is expected to reduce the global levels of H3K27me3 (histone H3 lysine 27 trimethylation), the repressive epigenetic mark deposited by EZH2. This leads to derepression of tumor suppressor genes and inhibition of cancer cell proliferation. The compound is a research agent for cancer studies, particularly in EZH2‑dependent cancers such as lymphomas and certain solid tumors. |
| Enzyme Assay |
General cell‑free assay for EZH2 PROTAC ternary complex formation: Use TR‑FRET or AlphaLISA to detect the interaction between EZH2 (as part of PRC2 complex) and the E3 ligase (e.g., CRBN or VHL) in the presence of NUCC-0226272. Purify PRC2 complex containing EZH2, EED, and SUZ12. Label EZH2 with a donor fluorophore and the E3 ligase ligand with an acceptor. Add varying concentrations of NUCC-0226272 (0.1 nM to 10 uM). Measure the FRET signal to determine the EC₅0 for ternary complex formation, indicating PROTAC‑mediated bridging.
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| Cell Assay |
General cellular degradation protocol for EZH2: Seed EZH2‑dependent cancer cells (e.g., lymphoma cell lines SU‑DHL‑4 or KARPAS‑422) in 6‑well plates. Treat cells with NUCC-0226272 at concentrations ranging from 0.1 nM to 1 uM for 24‑72 hours. Harvest cells, lyse, and quantify protein. Perform SDS‑PAGE and Western blot with anti‑EZH2, anti‑H3K27me3, and anti‑GAPDH (loading control). Calculate DC₅0 and Dmax values. Assess cell viability using CellTiter‑Glo assay after 72 hours. For rescue experiments, co‑treat with the proteasome inhibitor MG132 (10 uM, 4‑6 hours) to confirm proteasome‑dependent degradation.
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| Animal Protocol |
General animal protocol for EZH2 PROTACs: Establish subcutaneous xenografts of EZH2‑dependent cancer cells (e.g., SU‑DHL‑4 lymphoma or EZH2‑mutant cancer cells) in immunocompromised mice (NOD/SCID). When tumors reach ~150 mm3, randomize mice (n=8/group). Administer NUCC-0226272 via intraperitoneal injection at doses of 5‑30 mg/kg daily or every other day for 2‑3 weeks. Measure tumor volume twice weekly. At study end, harvest tumors for Western blot (EZH2, H3K27me3), qPCR (target gene expression), and immunohistochemistry (Ki‑67, cleaved caspase‑3).
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| ADME/Pharmacokinetics |
General pharmacokinetic protocol for NUCC-0226272: Administer the PROTAC to male Sprague‑Dawley rats via intravenous (IV, 1 mg/kg) and intraperitoneal (IP, 10 mg/kg) routes. Formulate in appropriate vehicle (e.g., 10% DMSO, 50% PEG400, 40% saline). Collect blood samples at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours. Analyze plasma concentrations by validated LC‑MS/MS method. Calculate PK parameters (Cmax, Tmax, AUC, t1/2, clearance, volume of distribution). PROTACs typically have high molecular weights (>1000 Da) and may exhibit low oral bioavailability.
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| Toxicity/Toxicokinetics |
General toxicity studies for NUCC-0226272: Perform a 14‑day repeated dose toxicity study in mice or rats. Administer NUCC-0226272 intraperitoneally at doses of 10, 30, and 100 mg/kg/day. Monitor body weight, food consumption, and clinical signs daily. At termination, collect blood for hematology (complete blood count) and serum chemistry (ALT, AST, BUN, creatinine, ALP). Perform gross necropsy and collect major organs (liver, kidney, spleen, lung, heart, gastrointestinal tract) for histopathological examination. Assess potential off‑target degradation by proteomics analysis.
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| References | |
| Additional Infomation |
NUCC-0226272 is a potent PROTAC that targets EZH2 for degradation. The compound has a molecular weight of 1182.56 and is stored as a powder at ‑20degC. EZH2 is a well‑validated oncology target, and PROTAC‑mediated degradation offers an advantage over enzymatic inhibition by removing both catalytic and non‑catalytic functions of the protein. The compound has the potential for cancer research, particularly in hematological malignancies and solid tumors with EZH2 activating mutations or overexpression.
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| Molecular Formula |
C67H91N9O8S
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| Molecular Weight |
1182.56
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| CAS # |
3004503-12-9
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| Appearance |
Solid powder
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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) |
DMSO : ≥ 140 mg/mL (118.39 mM)
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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 | 0.8456 mL | 4.2281 mL | 8.4562 mL | |
| 5 mM | 0.1691 mL | 0.8456 mL | 1.6912 mL | |
| 10 mM | 0.0846 mL | 0.4228 mL | 0.8456 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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