AS-605240
(Synonyms: 5-(6-喹喔啉亚甲基)-2,4-噻唑啉二酮) 目录号 : GC12474
A potent inhibitor of PI3-kinase γ
Cas No.:648450-29-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. | |
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.
| Cas No. | 648450-29-7 | SDF | |
| 别名 | 5-(6-喹喔啉亚甲基)-2,4-噻唑啉二酮 | ||
| 化学名 | (5Z)-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidine-2,4-dione | ||
| Canonical SMILES | C1=CC2=NC=CN=C2C=C1C=C3C(=O)NC(=O)S3 | ||
| 分子式 | C12H7N3O2S | 分子量 | 257.27 |
| 溶解度 | ≥ 4.28mg/mL in DMSO with gentle warming, <2.45 mg/mL in EtOH, <2.43 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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