AS1949490 is an orally bioactive and selective SHIP2 phosphatase inhibitor, with IC50s of 0.34, 0.62, and 0.62 for inhibiting mouse SHIP2, human SHIP2, human SHIP1, human PTEN, human synaptic vesicle phosphatase, and human myotubular protein, respectively. 13, >50, >50 and >50 µM. AS1949490 increases Akt phosphorylation, glucose consumption, and glucose uptake. AS1949490 activates the intracellular insulin signaling pathway. AS1949490 may be utilized in diabetes research.

Physicochemical Properties

Molecular Formula	C20H18CLNO2S
Molecular Weight	371.879
Exact Mass	371.075
CAS #	1203680-76-5
PubChem CID	44473434
Appearance	White to off-white solid powder
LogP	6.046
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	422
Defined Atom Stereocenter Count	1
SMILES	C[C@@H](C1=CC=CC=C1)NC(=O)C2=C(C=CS2)OCC3=CC=C(C=C3)Cl
InChi Key	RFZPGNRLOKVZJY-AWEZNQCLSA-N
InChi Code	InChI=1S/C20H18ClNO2S/c1-14(16-5-3-2-4-6-16)22-20(23)19-18(11-12-25-19)24-13-15-7-9-17(21)10-8-15/h2-12,14H,13H2,1H3,(H,22,23)/t14-/m0/s1
Chemical Name	3-[(4-chlorophenyl)methoxy]-N-[(1S)-1-phenylethyl]thiophene-2-carboxamide
Synonyms	AS1949490 AS 1949490 AS-1949490
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

ln Vitro	Insulin-induced Akt phosphorylation in L6 myotubes is increased by AS1949490 (0-16 μM; 15 minutes) [1]. In L6 myotubes, AS1949490 (0-10 μM; 48) induces stress and promotes trophic activity [1]. AS1949490 (0-0.10 μM; 24-hour; L6 myotubes) inhibits the gluconeogenic process triggered by insulin [1]. In L6 myotubes, AS1949490 (10 μM; 48 hours) upregulates the GLUT1 gene to initiate oxygen switching [2].
ln Vivo	The intracellular insulin signaling pathway is activated and the risk of diabetes in the diabetic retina is decreased by AS1949490 (300 mg/kg; Pathway; twice daily for 7 or 10 days) [1]. AS1949490 (300 mg/kg; 8-hour single dose).
Cell Assay	Western Blot Analysis [1] Cell Types: L6 Myotubes Tested Concentrations: 0, 4, 8 and 16 μM; ]. 1 nM (insulin) Incubation Duration: 15 minutes Experimental Results: Insulin-induced Akt phosphorylation increases in a dose-dependent manner. Western Blot Analysis[2] Cell Types: L6 myotubes Tested Concentrations: 10 µM Incubation Duration: 48 hrs (hours) Experimental Results: GLUT1 mRNA expression was increased in L6 myotubes, but GLUT4 mRNA expression was not.
Animal Protocol	Animal/Disease Models: Male C57BL/KsJ Jcl-dbm mice and db/+db mice [1]. Doses: 300 mg/kg. Route of Administration: oral; ; formulated ICR s) Inhibit gluconeogenesis and the expression of related genes [1]. twice (two times) daily for 7 or 10 days Experimental Results: Decrease in plasma glucose (23% relative to vehicle). Reduction in fasting blood glucose (37% relative to vehicle) and area under the blood glucose concentration-time curve (AUC). Increases GSK3β phosphorylation in the liver without changing overall GSK3β protein levels. Animal/Disease Models: Male ICR mice (6 weeks old) [1] Doses: 300 mg/kg Route of Administration: po (po (oral gavage)) once for 8 hrs (hrs (hours)). Experimental Results: PEPCK and G6Pase mRNA levels were diminished by approximately 50%.
References	[1]. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87. [2]. Glucose metabolism activation by SHIP2 inhibitors via up-regulation of GLUT1 gene in L6 myotubes. Eur J Pharmacol. 2010 Sep 10;642(1-3):177-82.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~134.45 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6890 mL	13.4452 mL	26.8904 mL
	5 mM	0.5378 mL	2.6890 mL	5.3781 mL
	10 mM	0.2689 mL	1.3445 mL	2.6890 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.