AS-605240 |
| Catalog No.GC12474 |
Potent and selective PI 3-Kγ inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 648450-29-7
Sample solution is provided at 25 µL, 10mM.
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AS-605240 is a selective PI3K γ inhibitor with an IC50 of 8 nM. [1]
PI3Ks are a family of enzymes, which phosphorylate the 3’- OH position of the inositol ring of phosphoinositides.They have been divided into three classes on the basis of structural features and in vitro lipid substrate specificity. The three class-Ia PI3-kinases (p110 α / β / δ ) and the sole class-Ib PI 3-kinase (p110 γ ) couple growth factor receptors and G-protein-coupled receptors, respectively, to a wide range of downstream pathways. Signal transduction via the PI3K/Akt pathway is essential for regulating cellular responses, including proliferation, survival, migration, motility and tumorigenesis, in a variety of cell types. The key selectivity features were identified by co-crystallization with PI3Kγ, which revealed that thiazolidinedione nitrogen makes a salt – bridge interaction with the side chain of Lys-833, and also forms the link to Val-882.[1,2]
AS-605240 is a cell permeable inhibitor for PI3Ks and inhibits p110 α/β/γ/δ in vitro?with IC50 values of 0.06, 0.27, 0.008 0.3 μΜ, respectively. AS-605240 was tested its ability to inhibit C5a-mediated PKB phosphorylation in RAW264 mouse macrophages and AS-605240 showed an IC50 of 0.09 mM. [1]
As in many in?ammatory processes, neutrophils are predominant in the initial in?ux of leukocytes, followed by monocytes-macrophages and lymphocytes. in vivo efficacy in blocking leukocyte migration assays were conducted, AS-605240 was tested in two different mouse models of peritonitis, including RANTES-induced or thioglycollate, the outcome showed ED50 of 9.1 mg/kg and 10 mg/kg respectively. AS-605240 also show that it is an orally active, selective PI3Kγ inhibitor suppresses joint inflammation and damage in a mouse model of collagen-induced arthritis.[1]
References:
[1]. Camps M, Rückle T, Ji H, et al. Blockade of PI3Kγ suppresses joint inflammation and damage in mouse models of rheumatoid arthritis[J]. Nature medicine, 2005, 11(9): 936-943.
[2]. Marone R, Cmiljanovic V, Giese B, et al. Targeting phosphoinositide 3-kinase—moving towards therapy[J]. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2008, 1784(1): 159-185.
Kinase experiment: | Human PI3Kγ (100 ng) is incubated at RT with kinase buffer (10 mM MgCl2, 1 mM β-glycerophosphate, 1 mM DTT, 0.1 mM Na3VO4, 0.1% Na Cholate and 15 M ATP/100 nCi γ[33P]ATP, final concentrations) and lipid vesicles containing 18 M PtdIns and 250 M of PtdSer (final concentrations), in the presence of inhibitors or DMSO. Kinase reaction is stopped by adding 250 g of Neomycin-coated Scintillation Proximity Assay (SPA) bead and proceeded. |
Cell experiment: | A total of 5×105 BDC2.5 splenocytes and 50 μg/mL BDC2.5-peptide are incubated in vitro in a 96-well round-bottom plate for 48 h. Then the cultures are pulsed with 1 μCi of tritiated thymidine [3H] to determine cell proliferation. |
Animal experiment: | In this study, rats are bred for one week to affirm body weight and then randomLy divided into four experimental groups: (a) control group (rats are given vehicle only); (b) BLM group (rats are induced with BLM); (c) BLM + 25 mg/kg AS605240 group (rats are induced with BLM and then administrated with 25 mg/kg AS605240); (d) BLM + 50 mg/kg AS605240 group (the same protocol as the former group except a different dose of 50 mg/kg AS605240). In addition, five rats are given 50 mg/kg AS605240 only to detect whether AS605240 has any side effect simultaneously as the previous four groups. Rats in (c), (d) and AS605240-given-only group are administered orally 25, 50 and 50 mg/kg AS605240 by gavage while rats in control group and BLM group are given only equivalent saline at day-1 (the day rats are given BLM is marked as day-0). The same dosage is maintained once everyday for 28 days. |
References: [1]. Huang X, et al. Endothelial p110γPI3K Mediates Endothelial Regeneration and Vascular Repair After Inflammatory Vascular Injury. Circulation. 2016 Mar 15;133(11):1093-103. | |
| Cas No. | 648450-29-7 | SDF | |
| Chemical Name | (5Z)-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidine-2,4-dione | ||
| Canonical SMILES | C1=CC2=NC=CN=C2C=C1C=C3C(=O)NC(=O)S3 | ||
| Formula | C12H7N3O2S | M.Wt | 257.27 |
| Solubility | ≥ 4.28mg/mL in DMSO with gentle warming, <2.45 mg/mL in EtOH, <2.43 mg/mL in Water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.887 mL | 19.4348 mL | 38.8697 mL |
| 5 mM | 0.7774 mL | 3.887 mL | 7.7739 mL |
| 10 mM | 0.3887 mL | 1.9435 mL | 3.887 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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