| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
RKIP[3]
(E/Z)-Locostatin targets Raf kinase inhibitor protein (RKIP), a protein that regulates multiple signaling pathways including the Raf-MEK-ERK cascade and G protein-coupled receptor signaling. By binding to Raf kinase and inhibiting RKIP, Locostatin disrupts the interaction of RKIP with Raf-1 kinase and G protein-coupled receptor kinase 2. This disruption modulates downstream signaling pathways involved in cell proliferation, migration, and survival. |
|---|---|
| ln Vitro |
In vitro, Locostatin inhibits cell proliferation/growth and migration. As a cell-permeable compound, it effectively enters cells and disrupts RKIP/Raf1 kinase interactions. The compound's activity is concentration-dependent, with effects observed at micromolar concentrations. Locostatin has been used in various cellular assays to study the role of RKIP in cell migration, proliferation, and signaling. Its racemic form (E/Z)-Locostatin is used as a tool compound in these studies.
|
| ln Vivo |
In vivo, Locostatin exacerbates thioacetamide-induced acute liver failure in mice. This effect is mediated through its inhibition of RKIP and disruption of RKIP/Raf1 kinase interactions, which modulates signaling pathways involved in liver injury and regeneration. The compound has been studied in animal models to understand the role of RKIP in liver pathophysiology. However, detailed in vivo efficacy data are limited.
|
| Enzyme Assay |
Non-cell-based assays for (E/Z)-Locostatin involve binding studies to measure its interaction with Raf kinase and RKIP. Surface plasmon resonance or isothermal titration calorimetry can be used to measure binding affinity. Competitive binding assays with labeled probes are used to assess binding specificity. The compound's chemical properties are characterized by NMR, MS, and HPLC. Purity is determined by HPLC. The compound's stability in various solvents is characterized.
|
| Cell Assay |
Cellular assays for (E/Z)-Locostatin are performed using various cell lines. Cells are treated with Locostatin at various concentrations, and cellular responses are measured. Cell proliferation is measured by MTT or CellTiter-Glo assays. Cell migration is assessed by Transwell or scratch wound assays. RKIP/Raf1 interaction is evaluated by co-immunoprecipitation or proximity ligation assays. Downstream signaling pathways including Raf-MEK-ERK are assessed by Western blot.
|
| Animal Protocol |
In vivo experiments with Locostatin are conducted in animal models of liver injury. Mice are treated with thioacetamide to induce acute liver failure, and Locostatin is administered via intraperitoneal or intravenous injection. Liver injury is assessed by measuring serum transaminases (ALT, AST), histological analysis of liver tissues, and assessment of inflammatory markers. Survival is monitored. The exacerbation of liver failure by Locostatin is evaluated.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of (E/Z)-Locostatin have not been extensively characterized. As a small molecule with a molecular weight of 245.27, the compound is expected to have moderate oral bioavailability. Its cell-permeable nature suggests good membrane penetration. Its absorption, distribution, metabolism, and excretion are not well-defined. Comprehensive PK studies are needed to support further development.
|
| Toxicity/Toxicokinetics |
The toxicity profile of (E/Z)-Locostatin has not been comprehensively evaluated. As a tool compound used in research, its toxicity has been studied in the context of its effects on liver injury. Locostatin exacerbates thioacetamide-induced acute liver failure in mice, indicating potential hepatotoxicity. Comprehensive toxicological studies including genotoxicity, organ toxicity, and maximum tolerated dose have not been fully characterized. The compound is for research use only.
|
| References |
|
| Additional Infomation |
(E/Z)-Locostatin (CAS# 133812-16-5) is the racemate of Locostatin with the molecular formula C₁₄H₁₅NO₃ and a molecular weight of 245.27. It is also known as (E/Z)-UIC-1005 and (S)-(+)-4-Benzyl-3-crotonoyl-2-oxazolidinone. Locostatin is a cell-permeable, potent inhibitor of Raf kinase inhibitor protein (RKIP)/Raf1 kinase interaction. It inhibits cell proliferation/growth and migration and exacerbates thioacetamide-induced acute liver failure in mice. As of current knowledge, (E/Z)-Locostatin is not approved as a therapeutic agent.
|
| Molecular Formula |
C14H15NO3
|
|---|---|
| Molecular Weight |
245.27
|
| Exact Mass |
245.105
|
| CAS # |
133812-16-5
|
| Related CAS # |
Locostatin;90719-30-5
|
| PubChem CID |
5702600
|
| Appearance |
White to off-white solid powder
|
| Density |
1.205g/cm3
|
| Boiling Point |
351ºC at 760mmHg
|
| Melting Point |
84-88ºC(lit.)
|
| Flash Point |
166.1ºC
|
| Vapour Pressure |
4.22E-05mmHg at 25°C
|
| Index of Refraction |
1.57
|
| LogP |
2.09
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
18
|
| Complexity |
345
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C/C=C/C(=O)N1[C@H](COC1=O)CC2=CC=CC=C2
|
| InChi Key |
UTZAFVPPWUIPBH-QSLRECBCSA-N
|
| InChi Code |
InChI=1S/C14H15NO3/c1-2-6-13(16)15-12(10-18-14(15)17)9-11-7-4-3-5-8-11/h2-8,12H,9-10H2,1H3/b6-2+/t12-/m0/s1
|
| Chemical Name |
(4S)-4-benzyl-3-[(E)-but-2-enoyl]-1,3-oxazolidin-2-one
|
| 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 |
| 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 (407.71 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.19 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 (10.19 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0771 mL | 20.3857 mL | 40.7714 mL | |
| 5 mM | 0.8154 mL | 4.0771 mL | 8.1543 mL | |
| 10 mM | 0.4077 mL | 2.0386 mL | 4.0771 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
