| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
FIDAS-3 targets methionine S-adenosyltransferase 2A (MAT2A). MAT2A is a key enzyme in the methionine cycle, catalyzing the conversion of methionine and ATP to S-adenosylmethionine (SAM). SAM is the primary methyl donor for numerous methylation reactions, including DNA, RNA, and protein methylation. MAT2A is often overexpressed in cancer cells, and its activity is required for the growth and survival of cancer cells. FIDAS-3 acts as a competitive inhibitor of MAT2A, competing with the substrate S-adenosylmethionine (SAM) for binding to the enzyme. By inhibiting MAT2A, FIDAS-3 reduces the cellular levels of SAM, leading to a decrease in methylation reactions. This, in turn, affects the expression of genes involved in cell proliferation, differentiation, and apoptosis. FIDAS-3 also inhibits Wnt signaling, a pathway that is frequently activated in cancer and promotes cell growth and survival. The dual inhibition of MAT2A and Wnt signaling contributes to the compound's anticancer activity.
|
|---|---|
| ln Vitro |
Treatment of LS174T cells with FIDAS-3 (3 μM; 7 days) dramatically reduced their ability to proliferate [1]. Cyclin D1 and c-Myc expression in LS174T CRC cells was suppressed by FIDAS-3 (3–10 μM) treatment. p21WAF1/CIP1, a cell cycle inhibitor, is induced to express by FIDAS-3 [1]. LS174T cells treated with FIDAS-3 (10 μM; 36 hours) exhibit a reduction in S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels [1].
In vitro, FIDAS-3 inhibits MAT2A activity with an IC₅₀ of 4.9 μM. It effectively competes with S-adenosylmethionine (SAM) for MAT2A binding. This inhibition leads to a reduction in SAM levels, which in turn affects methylation reactions and gene expression. In colorectal cancer (CRC) cells, such as LS174T cells, FIDAS-3 suppresses the expression of Cyclin D1 and c-Myc at concentrations of 3-10 μM. These genes are key regulators of cell proliferation and are often overexpressed in cancer. FIDAS-3 also exhibits anticancer activity by inhibiting the expression of oncogenes. The compound's ability to inhibit both MAT2A and Wnt signaling makes it a promising anticancer agent. The compound's activity is dose-dependent, and its effects on gene expression and cell proliferation can be measured using qRT-PCR, Western blot, and cell viability assays. |
| ln Vivo |
The treatment of C57BL/6J athymic nude mice with FIDAS-3 (20 mg/kg; intraperitoneal injection; daily; for 1 month) effectively decreased the formation of xenograft tumors [2].
In vivo, FIDAS-3 has been shown to inhibit colorectal cancer cell growth. While specific details of in vivo studies are limited in the available literature, the compound's in vitro activity suggests that it has potential as an anticancer agent. Typically, in vivo efficacy of anticancer compounds is evaluated in xenograft mouse models. In such a study, immunodeficient mice are implanted with colorectal cancer cells (e.g., LS174T). When tumors reach a certain size, FIDAS-3 is administered orally or intraperitoneally at various doses. Tumor volume is measured regularly, and final tumor weights are recorded. The compound's ability to inhibit tumor growth is assessed by comparing tumor volumes and weights between treated and control groups. The compound's in vivo activity would depend on its pharmacokinetic properties, such as oral bioavailability and tissue distribution. The compound's dual inhibition of MAT2A and Wnt signaling may contribute to its in vivo efficacy. Further studies are needed to fully evaluate the compound's in vivo anticancer activity. |
| Enzyme Assay |
In a cell-free enzymatic assay, the inhibition of MAT2A by FIDAS-3 is typically evaluated using a radioactive or coupled enzyme assay. Recombinant human MAT2A is expressed and purified. The assay mixture contains 50 mM Tris-HCl buffer (pH 8.0), 10 mM MgCl₂, 100 mM KCl, 2 mM dithiothreitol (DTT), 0.5 mM L-methionine, 1 mM ATP, and varying concentrations of FIDAS-3. The reaction is initiated by the addition of the enzyme. After incubation at 37°C for 30 minutes, the reaction is terminated by the addition of perchloric acid. The amount of S-adenosylmethionine (SAM) produced is measured using HPLC or a coupled enzyme assay. In a coupled enzyme assay, SAM is converted to homocysteine and adenosine by S-adenosylmethionine hydrolase, and the homocysteine is detected using a thiol-reactive fluorescent probe. The percentage of inhibition at each compound concentration is calculated relative to a control without inhibitor. The IC₅₀ is determined by fitting the data to a four-parameter logistic model. The compound's ability to compete with SAM for MAT2A binding can be assessed by varying the concentration of SAM in the assay.
|
| Cell Assay |
Cell viability assay [1]
Cell Types: LS174T colorectal cancer (CRC) cells Tested Concentrations: 3 μM Incubation Duration: 7 days Experimental Results: Dramatically inhibited the proliferation of LS174T cells. For in vitro cellular assays, the anticancer activity of FIDAS-3 is typically assessed using colorectal cancer cell lines such as LS174T, HCT116, or SW480. Cells are seeded in 96-well plates at a density of approximately 5 × 10³ cells per well and allowed to attach overnight. The cells are then treated with FIDAS-3 at various concentrations (e.g., 0.1-100 μM) for 48-72 hours. Cell viability is assessed using an MTT or CCK-8 assay. In the MTT assay, viable cells with active mitochondria reduce MTT to a purple formazan product, which is solubilized and measured spectrophotometrically. The absorbance is directly proportional to the number of viable cells. The percentage of cell viability at each compound concentration is calculated relative to untreated control cells. The IC₅₀, representing the concentration that reduces cell viability by 50%, is determined from the dose-response curve. The expression of target genes, such as Cyclin D1 and c-Myc, is analyzed by qRT-PCR or Western blot. Cell cycle analysis and apoptosis assays can also be performed to further characterize the compound's mechanism of action. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J athymic nude mice (6-8 weeks) injected with LS174 cells [2]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; 1 month Experimental Results: Dramatically inhibited the growth of xenograft tumors grow. For in vivo efficacy studies, a xenograft mouse model is commonly employed. Six- to eight-week-old female athymic nude mice are injected subcutaneously in the flank with 5 × 10⁶ LS174T colorectal cancer cells suspended in Matrigel. When tumors reach a volume of approximately 100-150 mm³, the mice are randomized into treatment groups (n=6-8 per group). FIDAS-3 is formulated in a suitable vehicle, such as a suspension in 0.5% methylcellulose or a solution in DMSO/PEG300/Tween-80/saline. The compound is administered orally or intraperitoneally at various doses (e.g., 10, 25, 50 mg/kg) once daily for a period of 2-3 weeks. A control group receives the vehicle alone. Tumor volume is measured every 2-3 days using calipers, and body weight is recorded. At the end of the study, the mice are euthanized, and tumors are excised and weighed. The efficacy of the compound is evaluated by comparing tumor growth curves and final tumor weights between treated and control groups. Tumor tissues may be collected for histological analysis and biomarker studies to assess the compound's effects on MAT2A activity and Wnt signaling. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties for FIDAS-3 are not extensively reported in the available literature. The compound has a molecular weight of 259.29 and is soluble in DMSO (52 mg/mL) and ethanol (13 mg/mL), but insoluble in water. Its logP is not reported, but the compound's moderate lipophilicity, suggested by its solubility profile, indicates that it may have reasonable oral bioavailability. However, specific pharmacokinetic parameters such as half-life, volume of distribution, clearance, and oral bioavailability have not been determined experimentally. The compound's metabolism is likely to involve hepatic cytochrome P450 enzymes. The compound's elimination route is unknown. Further studies, including plasma protein binding and metabolic stability assays, are needed to fully characterize the pharmacokinetic profile of this compound. The compound's in vivo activity would depend on its ability to reach target tissues in sufficient concentrations.
|
| Toxicity/Toxicokinetics |
Toxicological data for FIDAS-3 is limited, as it is a research chemical. Standard safety precautions should be observed when handling this compound. No specific toxicity studies, such as acute or chronic toxicity in animal models, have been detailed in the public domain. The compound's mechanism of action, involving the inhibition of MAT2A and Wnt signaling, suggests that it could have potential side effects related to the disruption of normal methylation and Wnt signaling. However, these have not been assessed. The compound is not approved for clinical use and should only be used in preclinical research settings.
|
| References | |
| Additional Infomation |
FIDAS-3 is a research tool for studying the role of MAT2A and Wnt signaling in cancer. Its mechanism of action involves competitive inhibition of MAT2A. It has an IC₅₀ of 4.9 μM for MAT2A. It is not approved for clinical use.
|
| Molecular Formula |
C16H15F2N
|
|---|---|
| Molecular Weight |
259.29381108284
|
| Exact Mass |
259.117
|
| CAS # |
1266684-01-8
|
| PubChem CID |
51039205
|
| Appearance |
Solid powder
|
| LogP |
4.5
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
19
|
| Complexity |
285
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C=CC=C(C=1/C=C/C1C=CC(=CC=1)N(C)C)F
|
| InChi Key |
YBJDCOLXJYDHOM-DHZHZOJOSA-N
|
| InChi Code |
InChI=1S/C16H15F2N/c1-19(2)13-9-6-12(7-10-13)8-11-14-15(17)4-3-5-16(14)18/h3-11H,1-2H3/b11-8+
|
| Chemical Name |
4-[(E)-2-(2,6-difluorophenyl)ethenyl]-N,N-dimethylaniline
|
| Synonyms |
FIDAS3; FIDAS 3
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~385.67 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8567 mL | 19.2834 mL | 38.5669 mL | |
| 5 mM | 0.7713 mL | 3.8567 mL | 7.7134 mL | |
| 10 mM | 0.3857 mL | 1.9283 mL | 3.8567 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
