Locostatin (UIC-1005) is a potent RKIP inhibitor. Locostatin binds to Raf kinase, inhibits RKIP protein, and disrupts the interaction of RKIP with Raf-1 kinase and G protein-coupled receptor kinase 2. Locostatin inhibits cell proliferation/growth and migration. Locostatin aggravates thioacetamide-induced acute liver failure in mice.

Physicochemical Properties

Molecular Formula	C14H15NO3
Molecular Weight	245.27
Exact Mass	197.105
CAS #	90719-30-5
Related CAS #	(E/Z)-Locostatin;133812-16-5
PubChem CID	5702600
Appearance	White to light yellow solid powder
Density	1.205 g/cm3
Boiling Point	351ºC at 760 mmHg
Melting Point	84-88ºC(lit.)
Flash Point	166.1ºC
LogP	1.298
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(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
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)

Biological Activity

Targets	RKIP[3]
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].
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].
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.
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.
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.

Solubility Data

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) (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. 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. 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	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.