| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
UHRF1, H3K9me3[1]
The molecular target of NV03 is the Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) protein. It specifically binds to the tandem Tudor domain (TTD) of UHRF1 with a dissociation constant (Kd) of 2.4 uM. By binding to this domain, NV03 blocks the recognition of the H3K9me3 histone mark, disrupting the ability of UHRF1 to bind to chromatin. |
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| ln Vitro |
In vitro, NV03 demonstrates a high binding affinity for the UHRF1 TTD, with a 2.1-fold higher affinity than its parent compound NV01. This binding antagonizes the interaction between UHRF1 and H3K9me3, an epigenetic mark important for DNA methylation maintenance and gene silencing. As a result, NV03 has anticancer activity and is used to study the functional role of the UHRF1-H3K9me3 axis in epigenetic regulation.
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| ln Vivo |
Specific in vivo efficacy data for NV03 is not detailed in the provided summaries. However, given its validated activity as an UHRF1 antagonist, it would be used in in vivo models to investigate the role of this protein in cancer. Its role as an E3 ligase ligand suggests it could be incorporated into PROTAC molecules to degrade target proteins in living organisms, demonstrating its utility in advanced therapeutic approaches.
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| Enzyme Assay |
Binding is assessed using a cell-free fluorescence polarization (FP) competition assay or isothermal titration calorimetry (ITC). In an FP assay, a fluorescently labeled H3K9me3 peptide is incubated with purified UHRF1 protein. Upon binding, the polarization increases. The compound is added to compete with the peptide, leading to a decrease in polarization. The Kd value is derived from this competition.
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| Cell Assay |
For cellular studies, cancer cell lines are treated with NV03. The primary endpoint is the disruption of the UHRF1-H3K9me3 interaction, which can be assessed by a chromatin immunoprecipitation (ChIP) assay to measure UHRF1 occupancy at gene loci. Alternatively, a cellular interaction assay can be used. The compound's anticancer activity can be evaluated by measuring cell viability using an MTT or CellTiter-Glo assay.
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| Animal Protocol |
To study the in vivo function of UHRF1, NV03 can be formulated for injection (e.g., IP injection in saline formulation) in tumor xenograft mouse models. Mice bearing tumors are treated with the compound or a vehicle control. Tumor volume is measured with calipers to assess antitumor efficacy. As the compound is also an E3 ligase ligand, it can be used as a building block to create PROTACs for in vivo degradation studies.
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| ADME/Pharmacokinetics |
The provided literature does not contain detailed absorption, distribution, metabolism, and excretion (ADME) data for NV03. However, it is noted to be soluble in DMSO at 33.33 mg/mL, which facilitates its use in both in vitro assays and the preparation of formulations for potential in vivo applications. It is stable when stored at 2-8degC in a desiccated environment.
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| Toxicity/Toxicokinetics |
There is no specific toxicological data presented for NV03 in the provided summaries. As a research tool for studying epigenetic mechanisms and as a building block for PROTACs, its safety profile is subject to ongoing evaluation. In standard in vitro assays, its anticancer activity is observed, and general toxicity would be monitored in any in vivo efficacy studies through animal body weight and behavior.
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| References | |
| Additional Infomation |
UHRF1 is a key epigenetic regulator that links DNA methylation and histone modifications. It is overexpressed in many cancers and is associated with poor prognosis. NV03 is a specific antagonist of the UHRF1-H3K9me3 interaction. This antagonism can disrupt epigenetic silencing mechanisms and has potential as an anticancer therapy. Additionally, NV03 serves as a versatile tool for PROTAC design, enabling the targeted degradation of UHRF1. It is currently in the preclinical stage of research.
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| Molecular Formula |
C19H27N5O2S
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|---|---|
| Molecular Weight |
389.5150
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| Exact Mass |
389.188
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| CAS # |
2448341-58-8
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| PubChem CID |
139291004
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
27
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| Complexity |
595
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C([H])=C([H])C2=C1C(C([H])([H])[H])=C1C(N(C([H])([H])C(N([H])C([H])([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)N=C(C([H])([H])[H])N12)=O
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| InChi Key |
KNZQAVKYBBYDKV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H27N5O2S/c1-5-22(6-2)10-7-9-20-16(25)12-23-19(26)17-13(3)18-15(8-11-27-18)24(17)14(4)21-23/h8,11H,5-7,9-10,12H2,1-4H3,(H,20,25)
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| Chemical Name |
N-[3-(diethylamino)propyl]-2-(7,12-dimethyl-9-oxo-5-thia-1,10,11-triazatricyclo[6.4.0.02,6]dodeca-2(6),3,7,11-tetraen-10-yl)acetamide
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 33.33 mg/mL (85.57 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 | 2.5673 mL | 12.8363 mL | 25.6726 mL | |
| 5 mM | 0.5135 mL | 2.5673 mL | 5.1345 mL | |
| 10 mM | 0.2567 mL | 1.2836 mL | 2.5673 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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