| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
SMI481 targets Sec14-like phosphatidylinositol transfer proteins (PITPs), specifically the yeast PITP Sec14. Sec14 is a key regulator of phosphoinositide signaling, regulating membrane trafficking through the trans-Golgi network and endosomal systems. SMI481 selectively inhibits Sec14-mediated transfer of phosphatidylinositol (PtdIns). The compound's activity involves binding in the Sec14 hydrophobic cavity. This represents a new target for studying phosphoinositide signaling with more selectivity than lipid kinase-directed strategies. SMI481 is the first small-molecule inhibitor of this target class.
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| ln Vitro |
In vitro studies demonstrate that SMI481 is a selective inhibitor of the yeast PITP Sec14. The compound blocks Sec14-mediated transfer of [3H]-PtdIns in vitro with an IC50 of 0.21 μM. SMI481 also inhibits yeast growth with an IC50 of 2.87 μM. The compound's activity involves binding in the Sec14 hydrophobic cavity. As the first small-molecule Sec14-like PITP inhibitor, SMI481 provides a valuable tool for studying phosphoinositide signaling. The compound shows selectivity for Sec14 over other targets.
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| ln Vivo |
In vivo data for SMI481 is limited in the available literature. As an inhibitor of Sec14-like PITPs, the compound's effects on phosphoinositide signaling and membrane trafficking have been characterized primarily in yeast systems. The compound inhibits yeast growth with an IC50 of 2.87 μM, confirming its cellular activity. Sec14 is the sole essential NPPM target in yeast. Further studies in mammalian systems are warranted to evaluate the compound's effects on PITP function and phosphoinositide signaling.
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| Enzyme Assay |
The in vitro enzyme assay for SMI481 involves measuring Sec14-mediated phosphatidylinositol (PtdIns) transfer activity. Sec14 protein is incubated with liposomes containing [3H]-PtdIns and acceptor membranes in the presence of varying concentrations of SMI481 (1 nM-100 μM). The transfer of [3H]-PtdIns from donor to acceptor membranes is measured by scintillation counting or filter-binding methods. IC50 values are calculated from dose-response curves. For growth inhibition studies, yeast cells are cultured in liquid media with varying concentrations of SMI481 (0.1-100 μM) and growth is monitored by OD600 measurements. Binding affinity is assessed using isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR).
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| Cell Assay |
In vitro cellular assays for SMI481 use yeast cells (Saccharomyces cerevisiae) as the primary model system. Yeast cells are cultured in appropriate media and treated with the compound at concentrations of 0.1-100 μM for 1-24 hours. Cell growth is monitored by OD600 measurements. Phosphoinositide levels are measured by lipid extraction and mass spectrometry or thin-layer chromatography. Membrane trafficking is assessed using fluorescent protein markers for Golgi and endosomal compartments. Cell viability is assessed using plate assays or flow cytometry. The compound's selectivity is confirmed by testing in Sec14 mutant strains.
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| Animal Protocol |
In vivo animal studies for SMI481 are not extensively reported. As a yeast PITP inhibitor, the compound is primarily used for studying Sec14 function in yeast. For potential mammalian applications, studies would involve cell culture models or mouse models. The compound's activity in mammalian cells would need to be established. Based on its mechanism, SMI481 could be useful for studying phosphoinositide signaling and membrane trafficking in various biological contexts.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SMI481 are not extensively reported. The compound has a molecular weight of approximately 364.77 and molecular formula of C17H14ClFN4O3?. It is soluble in DMSO (30 mg/mL) and other organic solvents. The compound should be stored at -20°C for long-term preservation. Based on its physicochemical properties, the compound is expected to have reasonable membrane permeability. Further studies on oral bioavailability, plasma half-life, clearance, and protein binding are needed.
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| Toxicity/Toxicokinetics |
Toxicological data for SMI481 is not extensively reported. As a research compound intended for laboratory use only, it has not undergone comprehensive toxicological evaluation. Standard safety precautions should be followed when handling the compound. The compound is classified for research purposes only and should not be used for human therapeutic applications. For detailed toxicity information, specialized safety data sheets should be consulted.
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| References | |
| Additional Infomation |
SMI481 (NPPM6748481) is a research-grade compound with CAS number 432020-20-7. It is the first small-molecule inhibitor of Sec14-like phosphatidylinositol transfer proteins (PITPs). The compound selectively inhibits the yeast PITP Sec14, blocking PtdIns transfer (IC50 = 0.21 μM) and yeast growth (IC50 = 2.87 μM). It regulates membrane trafficking through the trans-Golgi network and endosomal systems. The compound is a valuable tool for studying phosphoinositide signaling. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only.
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| Molecular Formula |
C17H15CLFN3O3
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|---|---|
| Molecular Weight |
363.77
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| Exact Mass |
363.078
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| CAS # |
432020-20-7
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| PubChem CID |
1334619
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
543.3±50.0 °C at 760 mmHg
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| Flash Point |
282.4±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.625
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| LogP |
2.46
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
496
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LSPJXCGEFJDMHA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15ClFN3O3/c18-13-6-5-12(11-16(13)22(24)25)17(23)21-9-7-20(8-10-21)15-4-2-1-3-14(15)19/h1-6,11H,7-10H2
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| Chemical Name |
(4-chloro-3-nitrophenyl)-[4-(2-fluorophenyl)piperazin-1-yl]methanone
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| Synonyms |
NPPM 6748-481; SMI-481 SMI 481; SMI481
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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. |
| 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 (~274.90 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 | 2.7490 mL | 13.7449 mL | 27.4899 mL | |
| 5 mM | 0.5498 mL | 2.7490 mL | 5.4980 mL | |
| 10 mM | 0.2749 mL | 1.3745 mL | 2.7490 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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