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AS1949490

Alias: AS1949490 AS 1949490 AS-1949490
Cat No.:V7448 Purity: ≥98%
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.
AS1949490
AS1949490 Chemical Structure CAS No.: 1203680-76-5
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
50mg
Other Sizes
Official Supplier of:
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Product Description
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.
Biological Activity I Assay Protocols (From Reference)
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.

These protocols are for reference only. InvivoChem does not independently validate these methods.
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)
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.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Effect of AS1949490 on insulin-induced Akt phosphorylation in L6 myotubes. (A) Protein lysates from L6 myotubes were immunoblotted with anti-phosphorylated Akt antibody or anti-Akt antibody. L6 myotubes were incubated for 15 min both with (D,E) and without (B,C) AS1949490 treatment before being stimulated with insulin at indicated concentration (B) and 1 nM (D) or fetal bovine serum (FBS) at indicated concentrations (C,E) for 10 min. Signal output was converted to percent activation (D,E). The values are the means ± standard error of three independent experiments. Asterisks indicate significant differences: **P < 0.01, ***P < 0.001 versus 0 nM AS1949490 treatment.[1].Suwa A, et, al. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87.
  • Effect of AS1949490 on (A) glucose consumption and (B) glucose uptake in L6 myotubes, (C) gluconeogenesis in FAO cells and (D) hepatic gene expression in ICR mice. L6 myotubes were incubated with AS1949490 for 48 h under conditions conducive to differentiation. (A) Glucose consumption and (B) glucose uptake were then measured. The values are the means ± standard error (SE) of three independent experiments. FAO cells were treated with AS19494940 and insulin for 24 h. (C) The glucose concentration in the medium was measured after incubation for 6 h in gluconeogenesis buffer. The values are the means ± SE of four independent experiments. AS19494940 was administered to normal ICR mice at a dose of 300 mg·kg−1, p.o. after overnight fasting (n= 4 per group). After 8 h, the total RNA was isolated from the liver. (D) G6Pase and PEPCK mRNA levels were measured using real-time quantitative polymerase chain reaction. The values are the means ± SE (n= 4). Asterisks indicate significant differences: *P < 0.05, **P < 0.01, ***P < 0.001 versus 0 nM treatment with AS1949490 or vehicle.[1].Suwa A, et, al. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87.
  • Effect of chronic treatment with AS1949490 on (A,B) blood glucose during oral glucose tolerance tests (OGTT), and (C,D) phosphorylation of GSK3β in db/db mice. AS1949490 was given orally to db/db mice twice daily for 10 days at a dose of 300 mg·kg−1. Food was withheld for 16 h after the final drug dosing, and then glucose solution (2 g·kg−1) was loaded. (A) Blood glucose levels were measured at the indicated times before and after glucose loading (at time 0). (B) AUC levels during hours 0–2 of the OGTT were calculated for each group after subtracting the baseline values (time 0). The livers of the mice treated with AS1949490 were homogenized. (C) The liver protein lysates were immunoblotted with anti-phosphorylated GSK3β antibody or anti-GSK3β antibody. (D) The densitometric quantification of pGSK3β was normalized using the total GSK3β levels. The values of (A) and (B) are the means ± standard error (n= 8). Asterisks indicate significant differences: *P < 0.05, **P < 0.01 versus vehicle. The values shown in (D) are the means ± standard deviation for two animals.[1].Suwa A, et, al. Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2. Br J Pharmacol. 2009 Oct;158(3):879-87.
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