| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Snail/HDAC-IN-1 targets two key drivers of cancer metastasis and tumor progression: the Snail transcription factor and histone deacetylases (HDACs). Snail is a zinc-finger transcription factor that plays a critical role in epithelial-to-mesenchymal transition (EMT), a process essential for cancer cell invasion, migration, and metastasis. HDACs are enzymes that remove acetyl groups from histones, leading to chromatin condensation and transcriptional repression. By inhibiting both Snail and HDACs, this compound disrupts EMT and reprograms the epigenetic landscape of cancer cells, potentially reversing metastatic traits.
|
|---|---|
| ln Vitro |
Compound 9n, snail/HDAC-IN-1, exhibited antiproliferative action in the HCT-116 cell line, with an IC50 of 0.0751 μM. Good inhibitory effects are demonstrated by snail/HDAC-IN-1 on NCI-H522 (GI50=0.0488 μM), MDA-MB-435 (GI50=0.0361 μM), and MCF7 (GI50=0.0518 μM) [1].
In vitro, Snail/HDAC-IN-1 demonstrates potent inhibition of HDAC1 with an IC50 of 0.405 μM and potent inhibition against Snail with a Kd of 0.18 μM. The compound increases histone H4 acetylation and reduces Snail protein expression in HCT-116 cells. It induces apoptosis and inhibits the proliferation of cancer cells. The compound's activity is concentration-dependent, with effective concentrations typically in the low micromolar range. Its dual-targeting mechanism makes it a valuable tool for studying EMT, epigenetics, and cancer metastasis. |
| ln Vivo |
In vivo, Snail/HDAC-IN-1 has been studied in preclinical models of solid tumors. The compound's ability to inhibit Snail and HDACs may lead to reduced tumor growth and metastasis. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying EMT, epigenetics, and cancer biology. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
|
| Enzyme Assay |
The in vitro HDAC1 inhibition assay for Snail/HDAC-IN-1 typically uses purified HDAC1 enzyme and a fluorogenic substrate (e.g., Boc-Lys(Ac)-AMC). The assay is performed in 96-well plates with the enzyme, substrate, and varying concentrations of the test compound (typically 0.1 nM to 10 µM) at 37°C for 30-60 minutes. The reaction is terminated by adding a developer solution containing trypsin, and fluorescence is measured at excitation/emission wavelengths of 360/450 nm. IC50 values are calculated from dose-response curves using nonlinear regression. For Snail binding assays, surface plasmon resonance (SPR) or fluorescence polarization is used to measure the Kd. Positive controls (e.g., known HDAC inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
|
| Cell Assay |
For in vitro cellular assays, cancer cell lines (e.g., HCT-116 colon cancer cells) are treated with Snail/HDAC-IN-1 at concentrations ranging from 0.01 to 10 µM for 24-72 hours. Histone H4 acetylation is assessed by Western blotting. Snail protein expression is assessed by Western blotting or immunofluorescence. Cell viability is assessed using CellTiter-Glo or MTT assays. Cell migration and invasion are evaluated using wound-healing and Transwell assays. EMT markers (E-cadherin, vimentin, N-cadherin) are assessed by Western blotting or qRT-PCR. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls and are performed in triplicate.
|
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are subcutaneously inoculated with cancer cells (e.g., HCT-116 or other solid tumor cell lines). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). Snail/HDAC-IN-1 is administered orally or intraperitoneally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis of Snail, HDAC1, and EMT markers, as well as for immunohistochemistry (Ki67, E-cadherin, vimentin). Pharmacodynamic studies confirm target engagement and pathway modulation. All animal procedures are conducted in accordance with institutional guidelines.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Snail/HDAC-IN-1 have been partially characterized. The compound has a molecular weight of 488.54 and a molecular formula of C24H21FN8OS. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 4-8 hours. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate to high. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Further PK studies are needed for comprehensive characterization.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies of Snail/HDAC-IN-1 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
|
| References | |
| Additional Infomation |
Snail/HDAC-IN-1 (CYD19) is a potent dual-target inhibitor of Snail (Kd = 0.18 μM) and HDAC1 (IC50 = 0.405 μM). It increases histone H4 acetylation, reduces Snail expression, and induces apoptosis. The compound is used for studying solid tumors, EMT, and epigenetics. It is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥95%) for laboratory use only. Its dual-targeting mechanism makes it a valuable tool for studying cancer metastasis and for developing novel anticancer therapeutics.
|
| Molecular Formula |
C24H21FN8OS
|
|---|---|
| Molecular Weight |
488.54
|
| Exact Mass |
488.154
|
| CAS # |
2415281-52-4
|
| PubChem CID |
153528580
|
| Appearance |
Light yellow to light brown solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
35
|
| Complexity |
713
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(NC1=CC=C(F)C=C1N)(=O)C1=CC=C(CSC2N=C(NC3C=C(C)NN=3)C3=CC=CN3N=2)C=C1
|
| InChi Key |
FWJQLBLNLGDLIU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H21FN8OS/c1-14-11-21(31-30-14)28-22-20-3-2-10-33(20)32-24(29-22)35-13-15-4-6-16(7-5-15)23(34)27-19-9-8-17(25)12-18(19)26/h2-12H,13,26H2,1H3,(H,27,34)(H2,28,29,30,31,32)
|
| Chemical Name |
N-(2-amino-4-fluorophenyl)-4-[[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylmethyl]benzamide
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.0469 mL | 10.2346 mL | 20.4692 mL | |
| 5 mM | 0.4094 mL | 2.0469 mL | 4.0938 mL | |
| 10 mM | 0.2047 mL | 1.0235 mL | 2.0469 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
