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| 10mg |
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| Targets |
STC-15 specifically targets the RNA methyltransferase METTL3. It inhibits the enzymatic activity of METTL3, which is responsible for installing the m6A modification on mRNA. By blocking this key epitranscriptomic regulator, the compound alters gene expression programs, leading to increased interferon signaling and the activation of anti-cancer immune responses. This molecular targeting is a novel approach in cancer immunotherapy.
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| ln Vitro |
In vitro, STC-15 treatment (0.5 uM; 48 h) induces the expression of endogenous interferon (IFN) signaling in cancer cell lines, such as the Caov3 ovarian cell line. This indicates its ability to activate an anti-tumor immune gene program. The compound inhibits tumor growth by activating anti-cancer immune responses and is shown to synergize with T-cell checkpoint blockade, thereby enhancing the immune system's ability to fight cancer cells.
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| ln Vivo |
In vivo, STC-15 has demonstrated significant anti-tumor activity. In a syngeneic mouse model (e.g., MC38 colorectal cancer model), oral administration of STC-15 for 12 days led to a reduction in tumor volume compared to control mice. Its mechanism involves activating anti-cancer immune responses associated with increased interferon signaling, effectively inhibiting tumor growth and making it a promising candidate for cancer research, particularly in combination with immunotherapies.
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| Enzyme Assay |
A cell-free biochemical assay is used to measure METTL3 inhibition. Recombinant METTL3-METTL14 complex is incubated with a synthetic RNA substrate and a radiolabeled methyl donor, S-adenosyl-L-methionine (3H-SAM). After the reaction, the methylated RNA is captured on a filter or plate, and the amount of incorporated radioactivity is quantified by scintillation counting. The compound is added to the mixture to calculate its IC50 based on the reduction in methyl transfer.
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| Cell Assay |
For cellular assays, cancer cell lines (e.g., Caov3) are cultured and treated with serial dilutions of STC-15 for 48 hours. The level of m6A modification in total RNA is measured using an m6A ELISA-based kit to assess target engagement. Activation of the interferon signaling pathway is confirmed by analyzing the expression of ISG (Interferon-Stimulated Genes) using quantitative real-time PCR (qRT-PCR). Cell viability is determined using a standard assay like CellTiter-Glo.
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| Animal Protocol |
For in vivo efficacy studies, a syngeneic mouse model, such as the MC38 colorectal cancer model, is employed. Mice bearing established tumors are randomized into treatment groups. STC-15 is formulated for oral gavage, typically as a suspension in a vehicle like 0.5% methylcellulose. The compound is administered once or twice daily for a specified period (e.g., 12 days). Tumor volume is measured with calipers, and tumor-infiltrating lymphocytes are analyzed by flow cytometry to assess immune activation.
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| ADME/Pharmacokinetics |
STC-15 is described as an orally active compound, indicating it has favorable drug metabolism and pharmacokinetic (DMPK) properties. It can be formulated for oral administration (e.g., as a suspension in CMC-Na). The compound is soluble in DMSO at 125 mg/mL, facilitating in vitro use. In vivo, it can also be formulated in a 5% DMSO, 40% PEG300, 5% Tween-80, 50% ddH2O or 5% DMSO, 95% corn oil solution for injection if needed. Its half-life and bioavailability are proprietary but support its oral efficacy.
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| Toxicity/Toxicokinetics |
Specific toxicology data for STC-15 is not detailed in the provided literature. As a METTL3 inhibitor, its safety profile is an ongoing area of research. In the described in vivo model, the compound was tolerated at the efficacious dose. Its ability to activate interferon signaling could potentially lead to immune-related adverse effects, a common class effect for immunomodulatory agents. Standard laboratory safety precautions should be taken.
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| References | |
| Additional Infomation |
The mechanism of action of STC-15 is based on the emerging field of epitranscriptomics. By inhibiting METTL3, it reduces m6A modification of mRNA, which can alter the stability and translation of numerous transcripts, including those involved in immune signaling. This leads to the activation of the STING (Stimulator of Interferon Genes) pathway and enhanced anti-tumor immunity. STC-15 is a research tool; as of now, it is not approved for human use, but its novel mechanism makes it a candidate for potential clinical development in oncology.
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| Molecular Formula |
C24H25N5O2
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|---|---|
| Molecular Weight |
415.487604856491
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| Exact Mass |
415.2
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| CAS # |
2648257-56-9
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| PubChem CID |
156442379
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
841
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12C=CC=CN1C(=O)C=C(C(NCC1=CC3=C(C=C1)C=C(CNCC1CCC1)N3)=O)N=2
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| InChi Key |
MFQFZLWCFZZHAI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25N5O2/c30-23-12-21(28-22-6-1-2-9-29(22)23)24(31)26-14-17-7-8-18-11-19(27-20(18)10-17)15-25-13-16-4-3-5-16/h1-2,6-12,16,25,27H,3-5,13-15H2,(H,26,31)
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| Chemical Name |
N-[[2-[(cyclobutylmethylamino)methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-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 |
| 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: 125 mg/mL (300.85 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 | 2.4068 mL | 12.0340 mL | 24.0680 mL | |
| 5 mM | 0.4814 mL | 2.4068 mL | 4.8136 mL | |
| 10 mM | 0.2407 mL | 1.2034 mL | 2.4068 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05584111
Conditions:Advanced Cancer|Advanced Solid Tumor|CancerProducts are for research use only; We do not sell to patients
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