| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SUV39H1 (suppressor of variegation 3-9 homolog 1) methyltransferase. F5446 selectively inhibits SUV39H1, an enzyme responsible for the trimethylation of histone H3 at lysine 9 (H3K9me3). By inhibiting SUV39H1, F5446 reduces H3K9me3 levels at specific gene promoters, such as FAS. This epigenetic modulation leads to the reactivation of Fas expression, which is often silenced in cancer cells. The inhibition of CTL effector gene expression also contributes to its overall effect on the tumor microenvironment.
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| ln Vitro |
In vitro, F5446 induces cell death in human colon cancer cell lines such as SW620 and LS411N in a dose-dependent manner. At concentrations of 100-250 nM for 48 hours, it induces cell cycle arrest in the S phase. At concentrations ranging from 10 to 1000 nM, it induces apoptosis in a concentration-dependent manner. Normal human colon epithelial cells (CCD841) are less sensitive to F5446-induced apoptosis compared to tumor cells. It promotes apoptosis by increasing Fas expression through inhibition of H3K9me3 deposition on the FAS promoter.
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| ln Vivo |
In vivo activity data for F5446 are not detailed in the available literature. As a research compound, its primary characterization has been in vitro. The compound is a selective SUV39H1 inhibitor, and its mechanism suggests potential for in vivo efficacy in colorectal cancer models by restoring Fas-mediated apoptosis. However, specific in vivo studies, including animal model efficacy, pharmacokinetics, or toxicity, have not been reported in the available sources. Further investigation would be required to establish its in vivo antitumor activity and safety profile.
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| Enzyme Assay |
In vitro enzyme assays for F5446 involve measuring its inhibition of SUV39H1 methyltransferase activity. Typically, recombinant SUV39H1 enzyme is incubated with a histone H3 peptide substrate and a radiolabeled or fluorescent methyl donor (S-adenosylmethionine, SAM) in the presence of varying concentrations of F5446. The incorporation of methyl groups into the substrate is quantified, and the IC50 value is determined. Selectivity assays against other methyltransferases are performed to confirm specificity. Binding affinity may be assessed using surface plasmon resonance or isothermal titration calorimetry.
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| Cell Assay |
In vitro cell-based assays for F5446 are performed in colorectal cancer cell lines such as SW620 and LS411N. Cells are treated with F5446 at various concentrations (e.g., 10-1000 nM) for specified durations (e.g., 48 hours). Apoptosis is assessed by flow cytometry using Annexin V/PI staining. Cell cycle analysis is performed using propidium iodide (PI) staining and flow cytometry. Fas expression is measured by Western blot or flow cytometry. Cytotoxicity is evaluated using standard assays such as MTT or CellTiter-Glo. Normal cell lines like CCD841 are used as controls.
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| Animal Protocol |
Specific in vivo animal experimental protocols for F5446 are not described in the available literature. As a research compound, its in vivo profile has not been extensively published. If in vivo studies were to be conducted, they would likely involve subcutaneous xenograft models of colorectal cancer in immunocompromised mice. Tumor-bearing mice would be administered F5446 via oral gavage or intraperitoneal injection. Tumor volume, body weight, and survival would be monitored. Biomarkers such as H3K9me3 levels and Fas expression in tumor tissues would be assessed by immunohistochemistry or Western blot.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of F5446 have not been reported in the available literature. As a small molecule with a molecular weight of 552.94, it may have suitable properties for oral bioavailability, but this has not been confirmed. The compound is soluble in DMSO. Its stability, half-life, clearance, and volume of distribution are unknown. Any PK characterization would require standard studies involving intravenous and oral administration in rodents, with plasma concentration analysis by LC-MS/MS. These data are not currently available from public sources.
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| Toxicity/Toxicokinetics |
Toxicological data for F5446 are not detailed in the available literature. It is a research compound not intended for human use. In vitro, it demonstrates differential cytotoxicity, with tumor cells being more sensitive than normal colon epithelial cells. No LD50 values or repeated-dose toxicity studies have been reported. Standard safety pharmacology studies have not been performed. As with all research chemicals, appropriate safety precautions should be taken when handling. Specific toxicological endpoints have not been established.
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| References | |
| Additional Infomation |
F5446 is a selective SUV39H1 methyltransferase inhibitor. It promotes apoptosis in colorectal cancer cells by inhibiting H3K9me3 deposition on the FAS promoter and increasing Fas expression, while also suppressing CTL effector gene expression. Its molecular formula is C26H17ClN2O8S. It is an epigenetics compound with a purity of >98%. It is available for research purposes only and is not approved for clinical use.
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| Molecular Formula |
C26H17CLN2O8S
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|---|---|
| Molecular Weight |
552.939784765244
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| Exact Mass |
552.039
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| CAS # |
2304465-89-0
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| PubChem CID |
138482841
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| Appearance |
Orange to reddish brown solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
38
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)C1=CC2=C(N1S(=O)(=O)C3=CC=C(C=C3)Cl)C(=O)C(=O)C4=C2C(=CN4)C(=O)OCC5=CC=CC=C5
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| InChi Key |
MLPQCOLPRPRADV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H17ClN2O8S/c1-36-26(33)19-11-17-20-18(25(32)37-13-14-5-3-2-4-6-14)12-28-21(20)23(30)24(31)22(17)29(19)38(34,35)16-9-7-15(27)8-10-16/h2-12,28H,13H2,1H3
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| Chemical Name |
8-O-benzyl 2-O-methyl 3-(4-chlorophenyl)sulfonyl-4,5-dioxo-6H-pyrrolo[3,2-e]indole-2,8-dicarboxylate
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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 (~180.85 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (3.62 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one),suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1.82 mg/mL (3.29 mM) in 10% Cremophor EL in PBS (add these co-solvents sequentially from left to right, and one by one),suspension solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8085 mL | 9.0426 mL | 18.0851 mL | |
| 5 mM | 0.3617 mL | 1.8085 mL | 3.6170 mL | |
| 10 mM | 0.1809 mL | 0.9043 mL | 1.8085 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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