| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
RKIP[3]
Locostatin targets Raf kinase inhibitor protein (RKIP). RKIP is a physiological inhibitor of the Raf-1 kinase, a key component of the MAPK/ERK signaling pathway. By binding to RKIP, locostatin disrupts its interaction with Raf-1 kinase. This relieves the inhibition of Raf-1, leading to the activation of the MAPK/ERK pathway. The compound also disrupts the interaction of RKIP with G protein-coupled receptor kinase 2. |
|---|---|
| ln Vitro |
Locostatin (200 µM; 37 °C; 6 hours) interferes with RKIP's ability to interact with GRK2 and Raf-1 [1]. The growth and migration of MDCK cells are inhibited by locostatin (50 µM; 0-48 hours) [2].
In vitro, locostatin binds to RKIP and inhibits its function. By disrupting the RKIP-Raf-1 interaction, it activates the MAPK/ERK signaling pathway. This can lead to changes in cell proliferation, differentiation, and migration. The compound is an inhibitor of cell migration. |
| ln Vivo |
In mice with thioacetamide-induced acute liver failure, locostatin (0.5 mg/kg; intraperitoneal injection; once daily for 7 days) exacerbates the condition[3].
In vivo, locostatin can be used to study the role of RKIP in various biological processes. By inhibiting RKIP, it can modulate MAPK/ERK signaling and affect tumor growth and metastasis. However, specific in vivo activity data are not detailed in the search results. |
| Enzyme Assay |
Non-cellular assays for locostatin involve studying its binding to RKIP. This can be assessed using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The compound's ability to disrupt the RKIP-Raf-1 interaction can be measured in pull-down assays.
|
| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: MDCK cells Tested Concentrations: 50 µM Incubation Duration: 0-48 h Experimental Results: Inhibited cell proliferation and sheet migration. Cell-based assays for locostatin involve studying its effects on RKIP function and MAPK/ERK signaling in cells. Cells can be treated with the compound, and the phosphorylation of downstream targets, such as ERK, can be assessed by Western blot. The effects on cell migration can be measured using wound healing or transwell assays. |
| Animal Protocol |
Animal/Disease Models: 6 weeks, 18-22 g, male ICR mice (TAA model; injected intraperitoneally (ip) with 300 mg/kg TAA one time/day for 2 days)[3]
Doses: 0.5 mg/kg Route of Administration: Ip; one time/day for 7 days Experimental Results: diminished the expression of RKIP, led to more severe damage, such as steatosis and hepatic lesions, increased the production of ROS in the liver and TNF-α, IL-6 and IL-1β in the sera of mice with acute liver injury, inhibited Nrf2 and HO-1 expression in the livers of mice, induced NF-κB activation in the livers of mice, increased the phosphorylation of JNK, p38 and ERK in liver tissues. In vivo animal experiments with locostatin would typically involve administering the compound to mice or rats to study its effects in disease models. Xenograft models of cancer could be used to evaluate its anti-tumor and anti-metastatic effects. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for locostatin have not been extensively reported. The compound is soluble in DMSO at ≥30 mg/mL.
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| Toxicity/Toxicokinetics |
No specific toxicity data have been reported for locostatin. As a research compound, it should be handled with standard laboratory safety precautions.
|
| References |
[1]. Beshir AB, et al. Locostatin Disrupts Association of Raf Kinase Inhibitor Protein With Binding Proteins by Modifying a Conserved Histidine Residue in the Ligand-Binding Pocket. For Immunopathol Dis Therap. 2011;2(1):47-58.
[2]. Mc Henry KT, et al. A non-antibacterial oxazolidinone derivative that inhibits epithelial cell sheet migration. Chembiochem. 2002 Nov 4;3(11):1105-11. [3]. Lin X, et al. Inhibition of RKIP aggravates thioacetamide-induced acute liver failure in mice. Exp Ther Med. 2018 Oct;16(4):2992-2998. |
| Additional Infomation |
An RKIP inhibitor that reduces cell migration
Locostatin is a research compound, not an approved drug. It is a potent inhibitor of RKIP and an inhibitor of cell migration. It is used as a tool to study the role of RKIP in the MAPK/ERK pathway and cell migration. |
| Molecular Formula |
C14H15NO3
|
|---|---|
| Molecular Weight |
245.27
|
| Exact Mass |
197.105
|
| CAS # |
90719-30-5
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| Related CAS # |
(E/Z)-Locostatin;133812-16-5
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| PubChem CID |
5702600
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| Appearance |
White to light yellow solid powder
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| Density |
1.205 g/cm3
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| Boiling Point |
351ºC at 760 mmHg
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| Melting Point |
84-88ºC(lit.)
|
| Flash Point |
166.1ºC
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| LogP |
1.298
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
|
| Heavy Atom Count |
18
|
| Complexity |
345
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C(C1C=CC=CC=1)[C@H]1COC(=O)N1C(=O)/C=C/C
|
| 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
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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 (407.71 mM)
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|---|---|
| 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) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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.
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