| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 8.6 nM (EZH2); 62 nM (EZH1)[1]. DC50: 140 nM (EZH2 in MDA-MB-453 cells)[1]
EZH2 (enhancer of zeste homolog 2; histone methyltransferase). |
|---|---|
| ln Vitro |
MS8815 demonstrates effectiveness in blocking the methyltransferase activity of EZH2 and EZH1 with IC50 values of 8.6 nM and 62 nM, respectively[1]. In MDA-MB-453 cells, MS8815 (0.1–1 μM) destroys EZH2 with a DC50 value of 140 nM[1]. In TNBC cells, MS8815 (1 μM; 48 h) causes substantial EZH2 degradation in a manner that is dependent on concentration, time, and proteasome activity[1]. Multiple TNBC cell lines and primary patient TNBC cells exhibit efficient growth suppression when treated with MS8815 (0.1-10 μM; 5 days)[1].
MS8815 inhibits the methyltransferase activity of EZH2 with an IC50 of 8.6 nM. It also shows inhibitory activity against EZH1 with an IC50 of 62 nM. In MDA-MB-453 cells, MS8815 degrades EZH2 with a DC50 of 140 nM at concentrations of 0.1-1 uM. The compound effectively suppresses cell growth in multiple TNBC cell lines (BT549 cell GI50=2.0 uM) and primary patient TNBC cells (Patient 515a cells GI50=1.4 uM). It induces robust, concentration-, time-, and proteasome-dependent degradation of EZH2. |
| ln Vivo |
No specific in vivo data found; please refer to general EZH2 PROTAC properties: In mouse xenograft models of triple-negative breast cancer, EZH2 PROTACs like MS8815 typically demonstrate significant tumor growth inhibition when administered intraperitoneally (IP) at doses of 25-100 mg/kg daily for 4 weeks (5 days per week). Tumor tissues show reduced EZH2 protein levels and decreased H3K27me3 (the histone mark catalyzed by EZH2), with associated downregulation of EZH2 target genes involved in cell cycle progression.
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| Enzyme Assay |
Assay: In vitro EZH2 methyltransferase inhibition assay. Protocol: Recombinant EZH2 complex (EZH2/EED/SUZ12) is incubated with varying concentrations of MS8815 (0.1-100 nM), 3H-S-adenosylmethionine (3H-SAM), and nucleosome or histone H3 substrate. 3H-methyl incorporation into substrate is measured by scintillation counting after capture on filter plates. IC50 is calculated as the concentration inhibiting 50% of methyltransferase activity.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MDA-MB-453 cells and BT549 cells Tested Concentrations: 0.3, 3 μM; 1μM Incubation Duration: 48 h; 24 h Experimental Results: Induced nearly complete degradation of EZH2 and demonstrated the most robust degradation at 0.3 μM. Induced EZH2 degradation in a time-and concentration-dependent manner. Induced EZH2 degradation through the UPS. Cell Proliferation Assay[1] Cell Types: BT549, MDA-MB-468, SUM159 and MDA-MB-453 cells Tested Concentrations: 0.1-10 μM Incubation Duration: 5 days Experimental Results: demonstrated superior cellular growth inhibition activity in a panel of TNBC cells. Cells: TNBC cell lines (BT549, MDA-MB-453) and primary patient TNBC cells. Protocol: For degradation studies, cells are treated with MS8815 at 0.1-1 uM for 24-48 hours. EZH2 protein levels are analyzed by Western blot. The DC50 (degradation concentration 50%) is calculated. For cell growth inhibition, cells are treated with MS8815 (0.1-10 uM) for 5 days, and viability is measured using WST-8/CCK-8 assays to determine GI50 values. Proteasome-dependence is confirmed by co-treatment with MG132 (proteasome inhibitor). |
| Animal Protocol |
Animal Model: TNBC xenograft mouse models (e.g., C4-2 bearing NCG mice). Protocol: Mice bearing subcutaneous TNBC tumors receive MS8815 via intraperitoneal (IP) injection at 25, 50, or 100 mg/kg per day for 28 days (5 days per week). Tumor volume is measured twice weekly. At study endpoint, tumor tissues are harvested for immunoblotting analysis of EZH2, H3K27me3, and downstream target gene expression. Body weight is monitored as a general toxicity indicator.
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| ADME/Pharmacokinetics |
No specific PK data found for MS8815; please refer to general PROTAC properties: PROTAC molecules typically have high molecular weights (>900 Da), leading to poor oral bioavailability and short plasma half-lives (1-4 hours) due to rapid clearance. They are usually administered intraperitoneally (IP) in preclinical studies. MS8815 has a molecular weight of 1154.51 Da, with high purity (99.95%).
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| Toxicity/Toxicokinetics |
No specific comprehensive toxicity data found; please refer to general EZH2 degrader properties: At efficacious doses (25-100 mg/kg IP), EZH2 degraders are generally tolerated in mice without significant body weight loss. However, on-target toxicities may include effects on normal stem cell populations and hematopoiesis, as EZH2 is essential for maintaining certain cell lineages. The compound is in preclinical research and not approved for human use.
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| References | |
| Additional Infomation |
MS8815 is a selective EZH2 PROTAC degrader that effectively degrades EZH2 in a concentration-, time-, and proteasome-dependent manner. It inhibits the growth of TNBC cells and primary patient TNBC cells. Compared to EZH2 methyltransferase inhibitors (which only block enzymatic activity), PROTAC degraders like MS8815 eliminate the entire EZH2 protein, potentially disrupting both catalytic and non-catalytic functions. It can be used for TNBC research.
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| Molecular Formula |
C65H87N9O8S
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|---|---|
| Molecular Weight |
1154.51
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| Exact Mass |
1153.639
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| CAS # |
2855085-25-3
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| PubChem CID |
165368931
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| Appearance |
White to off-white solid powder
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| Density |
1?+-.0.06 g/cm3(Predicted)
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| Boiling Point |
1245.7±65.0 °C(Predicted)
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| LogP |
8.1
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| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
83
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| Complexity |
2250
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCN(CC5)C(=O)CCCCCCCC(=O)N[C@H](C(=O)N6C[C@@H](C[C@H]6C(=O)NCC7=CC=C(C=C7)C8=C(N=CS8)C)O)C(C)(C)C
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| InChi Key |
AOIZISCRIVNZJJ-XWJFFXCMSA-N
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| InChi Code |
InChI=1S/C65H87N9O8S/c1-9-73(51-25-31-82-32-26-51)55-35-50(34-53(44(55)4)61(78)67-38-54-42(2)33-43(3)69-62(54)79)48-21-19-47(20-22-48)39-71-27-29-72(30-28-71)58(77)16-14-12-10-11-13-15-57(76)70-60(65(6,7)8)64(81)74-40-52(75)36-56(74)63(80)66-37-46-17-23-49(24-18-46)59-45(5)68-41-83-59/h17-24,33-35,41,51-52,56,60,75H,9-16,25-32,36-40H2,1-8H3,(H,66,80)(H,67,78)(H,69,79)(H,70,76)/t52-,56+,60-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[[9-[4-[[4-[3-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methylcarbamoyl]-5-[ethyl(oxan-4-yl)amino]-4-methylphenyl]phenyl]methyl]piperazin-1-yl]-9-oxononanoyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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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) |
DMSO : 120 mg/mL (103.94 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (2.82 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 32.5 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 | 0.8662 mL | 4.3308 mL | 8.6617 mL | |
| 5 mM | 0.1732 mL | 0.8662 mL | 1.7323 mL | |
| 10 mM | 0.0866 mL | 0.4331 mL | 0.8662 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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