| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg |
| Targets |
UZH2 targets METTL3 (methyltransferase-like 3), the catalytic subunit of the m6A methyltransferase complex. This complex is responsible for installing the m6A modification, the most prevalent internal modification on eukaryotic mRNAs. By inhibiting METTL3, UZH2 reduces the overall levels of m6A on RNA, thereby modulating the expression and function of m6A-modified transcripts.
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| ln Vitro |
Compound 22 (UZH2), with an EC50 of 0.85 μM, dose-dependently stabilizes METTL3 in MOLM-13 cells at 54°C for 1 hour at concentrations of 0–25 μM [1]. MOLM-13 and PC-3 are decreased by UZH2 (16 h). In cells, the EC50 and m6A/A ratio of polyadenylated RNA are 0.7 μM and 2.5 μM, respectively [1].
In vitro, UZH2 is a highly potent and selective METTL3 inhibitor. Its activity is characterized by a biochemical IC50 of 5 nM in a TR-FRET assay. It shows selectivity against other methyltransferases, including METTL1 and METTL16. In cellular assays, UZH2 reduces m6A levels, with reported cellular EC50 values of 0.7 μM (MOLM-13) and 2.5 μM (PC-3). |
| ln Vivo |
In vivo efficacy data for UZH2 is limited in publicly available sources, as it is primarily a research tool. However, its potent and selective inhibition of METTL3 makes it a valuable compound for studying the biological consequences of m6A depletion in animal models. Specific in vivo studies, including dosing regimens and animal models, would be detailed in the primary literature.
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| Enzyme Assay |
The inhibitory activity of UZH2 is assessed using in vitro biochemical assays, such as the TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay. In this cell-free system, the METTL3 enzyme is incubated with a substrate and varying concentrations of UZH2. The TR-FRET signal, which is proportional to the methylation reaction, is measured, and the IC50 is calculated from the dose-response curve.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MOLM-13 Cell Tested Concentrations: 0-25 μM Incubation Duration: 1h Experimental Results: Stabilizes METTL3 in a dose-dependent manner at 54 °C. The cellular activity of UZH2 is evaluated in various cell lines. Cells are treated with UZH2, and the compound's effect on global m6A levels is measured using specific assays, such as an m6A ELISA or LC-MS/MS. The impact on cell proliferation and viability can also be assessed. The cellular EC50, the concentration required to reduce m6A levels by 50%, is calculated. |
| Animal Protocol |
In animal studies, UZH2 would typically be administered to rodents to study the effects of METTL3 inhibition in vivo. The route of administration (e.g., oral, intraperitoneal) and dosing regimen would be determined based on its pharmacokinetic properties. Efficacy endpoints would depend on the disease model being studied and could include tumor growth inhibition or changes in disease biomarkers.
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| ADME/Pharmacokinetics |
UZH2 has a molecular weight of 513.63 and a formula of C27H37F2N7O. It is soluble in DMSO (13 mg/mL) and ethanol (3 mg/mL) but is insoluble in water. For in vivo administration, it can be formulated as a homogeneous suspension in a vehicle like CMC-Na. The powder should be stored at -20°C.
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| Toxicity/Toxicokinetics |
Formal toxicology data for UZH2 is not publicly available, as it is a research compound not intended for human therapeutic use. Its safety profile has not been established in comprehensive toxicology studies. As with all research chemicals, standard laboratory safety practices should be followed.
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| References | |
| Additional Infomation |
UZH2 (CAS: 2756566-45-5) is a highly potent and selective chemical probe for studying METTL3 and the m6A epitranscriptome. Its availability as a research tool has been crucial for advancing the understanding of RNA methylation in health and disease. It is a key compound for validating METTL3 as a therapeutic target and for exploring the potential of m6A modulation in various diseases, including cancer.
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| Molecular Formula |
C27H37F2N7O
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|---|---|
| Molecular Weight |
513.625792264938
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| Exact Mass |
513.302
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| CAS # |
2756566-45-5
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| PubChem CID |
156587343
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
37
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| Complexity |
783
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1CN(C2C=C(F)C(CN3CCC(C)(C)CC3)=CC=2F)CC2(CCN(C3=NC=NC(NC)=C3)CC2)N1
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| InChi Key |
GYWOVBUGFWWSJR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H37F2N7O/c1-26(2)4-8-34(9-5-26)15-19-12-21(29)22(13-20(19)28)36-16-25(37)33-27(17-36)6-10-35(11-7-27)24-14-23(30-3)31-18-32-24/h12-14,18H,4-11,15-17H2,1-3H3,(H,33,37)(H,30,31,32)
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| Chemical Name |
4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]-2,5-difluorophenyl]-9-[6-(methylamino)pyrimidin-4-yl]-1,4,9-triazaspiro[5.5]undecan-2-one
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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 : ~50 mg/mL (~97.35 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9469 mL | 9.7346 mL | 19.4693 mL | |
| 5 mM | 0.3894 mL | 1.9469 mL | 3.8939 mL | |
| 10 mM | 0.1947 mL | 0.9735 mL | 1.9469 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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