Home PI3K/Akt/mTOR PI3K inhibitor AS-605240

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AS-605240 PI3K inhibitor

Cat.No.S1410

AS-605240 selectively inhibits PI3Kγ with IC50 of 8 nM, over 30-fold and 7.5-fold more selective for PI3Kγ than PI3Kδ/β and PI3Kα in cell-free assays, respectively.
AS-605240 PI3K inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 257.27

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Quality Control

Batch: Purity: 99.85%
99.85

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
RAW264.7 cells Function assay Inhibition of MCP1-induced chemotaxis in mouse RAW264.7 cells, IC50=5.31 μM
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 1 mg/mL (3.88 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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Mass Concentration Volume Molecular Weight
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In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 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.

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Chemical Information, Storage & Stability

Molecular Weight 257.27 Formula

C12H7N3O2S

 Storage (From the date of receipt)
CAS No. 648450-29-7 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=CC2=NC=CN=C2C=C1C=C3C(=O)NC(=O)S3

Mechanism of Action

Features
The most potent member of a new class of PI3Kγ-selective inhibitors.
Targets/IC50/Ki
PI3Kγ
(Cell-free assay)
8 nM
PI3Kα
(Cell-free assay)
60 nM
PI3Kβ
(Cell-free assay)
270 nM
PI3Kδ
(Cell-free assay)
300 nM
In vitro
AS-605240 is an ATP-competitive PI3Kγ inhibitor, with Ki values of 7.8 nM. This compound is isoform-selective, for it also inhibits PI3Kα, β, and δ, with IC50 of 60, 270, and 300 nM, respectively. It inhibits C5a-mediated PKB phosphorylation with IC50 of 90 nM. In bone marrow-derived monocytes (BMDMs), this chemical (1 μM) blocks MCP-1- or CSF-1-induced PKB phosphorylation. At SC-CA1 synapses in mice, this compound (100 nM) eliminates NMDAR LTD, without affecting mGluR LTD, depotentiation, and LTP.
Kinase Assay
In vitro PI3K lipid kinase assay
(1) For PI3Kγ: 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 μM ATP/100 nCi γ[33P]ATP, final concentrations) and lipid vesicles containing 18 μM PtdIns and 250 μM of PtdSer (final concentrations), in the presence of AS-605240 or DMSO. Kinase reaction is stopped by adding 250 μg of Neomycin-coated Scintillation Proximity Assay (SPA) beads. (2) For PI3Kα, β, and δ: varying amounts of ATP are incubated with the different purified PI3K isoforms and saturating concentrations of PtdIns. Consequently, IC50 determinations with PI3Kα, β, and δ, to evaluate inhibitor selectivity are performed as follows: 60 ng of PI3Kα are incubated at RT with kinase buffer, as described for PI3Kγ (but containing 89 μM ATP/300 nCi γ[33P]ATP and no Na Cholate, instead) and lipid vesicles containing 212 μM PtdIns and 58 μM of PtdSer. 100 ng of PI3Kβ are incubated at RT with kinase buffer (containing 70 μM ATP/300 nCi γ[33P]ATP, 4 mM MgCl2 and no Na Cholate) and lipid vesicles containing 225 μM PtdIns and 45 μM of PtdSer. 90 ng of PI3Kδ are incubated with kinase buffer (containing 65 μM ATP/300 nCi γ[33P]ATP, 1 mM MgCl2, and no Na Cholate) and lipid vesicles containing 100 μM PtdIns and 170 μM of PtdSer. The reactions are stopped after 2 hours.
In vivo
In RANTES-induced mouse model of peritonitis, AS-605240 reduces neutrophil chemotaxis with ED50 of 9.1 mg/kg. In a αCII-induced arthritis, this compound (50 mg/kg) protects against αCII-IA symptom. In a mouse model of collagen-induced arthritis, this compound (50 mg/kg) also suppresses joint inflammation and damage. In an obesity-induced diabetes model (ob/ob mice), this compound (10 mg/kg) lowers blood glucose levels, significantly improves both insulin sensitivity and glucose tolerance without affecting body weight. This chemical (30 mg/kg) displays more profound effects with slightly less weight gain. Moreover, this compound reduces the abundance of ATMs and the circulating levels of MCP-1.
References

Applications

Methods Biomarkers Images PMID
Western blot p-AKT / AKT
S1410-WB1
25869207

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