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| Targets |
As an enantiomer of a METTL3 inhibitor, UZH1b targets the same binding site on the METTL3 protein but with drastically reduced affinity. METTL3 (Methyltransferase-like 3) is a key RNA N6-methyladenosine (m6A) methyltransferase that plays a crucial role in mRNA modification and regulation of gene expression. The compound shows essentially no significant binding or inhibition of this enzyme.
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| ln Vitro |
UZH1b is essentially inactive against METTL3 in biochemical assays, exhibiting an IC50 value of 28 uM. This is significantly higher (indicating much weaker activity) compared to its potent enantiomer UZH1a. This property makes it a valuable control for validating that observed biological effects are specifically due to METTL3 inhibition, rather than off-target effects of the compound's scaffold.
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| ln Vivo |
Specific in vivo data for UZH1b is not detailed in the provided literature. However, as an inactive enantiomer, it is typically used as a negative control in animal studies alongside its active counterpart UZH1a. It can be formulated and administered (e.g., via intraperitoneal injection) to serve as a benchmark for assessing the specific on-target efficacy and potential side effects of the active METTL3 inhibitor in disease models.
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| Enzyme Assay |
For a cell-free assay, the compound's inhibitory activity against recombinant METTL3 is evaluated. METTL3 (complexed with METTL14) is incubated with a biotinylated RNA substrate and 3H-S-adenosyl-L-methionine (3H-SAM). After the reaction, the RNA is captured on streptavidin plates, and the amount of incorporated 3H-methyl groups is measured by scintillation counting. The compound is included in the reaction to determine its half-maximal inhibitory concentration (IC50).
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| Cell Assay |
For cellular studies, cell lines expressing relevant targets are treated with UZH1b as a negative control. The protocol parallels that for active METTL3 inhibitors. Cells are seeded and incubated with the compound for 48-72 hours. Key readouts, such as global m6A RNA methylation levels (detected by ELISA), are measured to confirm the lack of biological effect. Cell viability can also be assessed using an MTT or CellTiter-Glo assay.
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| Animal Protocol |
A typical in vivo protocol would use UZH1b as a control in xenograft mouse models. Immunocompromised mice bearing tumors are treated with the compound or an active METTL3 inhibitor. UZH1b can be dissolved in a vehicle such as a mixture of DMSO, PEG300, Tween-80, and saline (e.g., 10:40:5:45). It is then administered via intraperitoneal (IP) injection. Tumor volume and animal body weight are monitored to assess efficacy and tolerability.
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| ADME/Pharmacokinetics |
Detailed ADME data for UZH1b is not available in the provided literature. As a small molecule (MW 558.71), it has properties suitable for in vivo studies. It is soluble in DMSO at 100 mg/mL, allowing for the preparation of concentrated stock solutions. For in vivo administration, it can be formulated in a mixture of DMSO, PEG300, Tween-80, and saline for injection, as is common for similar research compounds.
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| Toxicity/Toxicokinetics |
No specific toxicology data for UZH1b is presented in the provided summaries. In research use, its safety profile is assumed to be similar to that of its active counterpart, UZH1a. As an essentially inactive compound, it is expected to have minimal pharmacological side effects at standard research doses, making it suitable as a negative control. Standard laboratory safety precautions should be taken when handling.
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| References | |
| Additional Infomation |
UZH1b is a pure (S)-enantiomer that serves as a negative control for METTL3 inhibitors. Its primary value lies in its ability to help differentiate between target-specific and off-target effects in biological experiments. It is a critical tool compound for validating the function of METTL3-mediated RNA methylation in various diseases. It is not a clinical candidate and is strictly for research use only.
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| Molecular Formula |
C32H42N6O3
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|---|---|
| Molecular Weight |
558.714287281036
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| Exact Mass |
558.331
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| CAS # |
2814392-17-9
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| Related CAS # |
UZH1;2925713-02-4;UZH1a;2813577-78-3
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| PubChem CID |
162642621
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
41
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| Complexity |
828
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1(CCN(CC1)CC2=CC(=C(C=C2)C(=O)NC[C@]3(CCCN(C3)C4=NC=NC(=C4)NCC5=CC=CC=C5)O)O)C
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| InChi Key |
PWYRDVXYAOGDNK-YTTGMZPUSA-N
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| InChi Code |
InChI=1S/C32H42N6O3/c1-31(2)12-15-37(16-13-31)20-25-9-10-26(27(39)17-25)30(40)34-21-32(41)11-6-14-38(22-32)29-18-28(35-23-36-29)33-19-24-7-4-3-5-8-24/h3-5,7-10,17-18,23,39,41H,6,11-16,19-22H2,1-2H3,(H,34,40)(H,33,35,36)/t32-/m0/s1
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| Chemical Name |
N-[[(3S)-1-[6-(benzylamino)pyrimidin-4-yl]-3-hydroxypiperidin-3-yl]methyl]-4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-hydroxybenzamide
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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: 100 mg/mL (178.98 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 | 1.7898 mL | 8.9492 mL | 17.8984 mL | |
| 5 mM | 0.3580 mL | 1.7898 mL | 3.5797 mL | |
| 10 mM | 0.1790 mL | 0.8949 mL | 1.7898 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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