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AS-605240

Name: AS-605240
Brand: Selleck Chemicals
SKU: S1410
Rating: 5 (30 reviews)

Catalog No.S1410

For research use only.

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.

CAS No. 648450-29-7

Selleck's AS-605240 has been cited by 30 publications

Purity & Quality Control

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PI3K Signaling Pathway Map

Biological Activity

Description

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.

Features

The most potent member of a new class of PI3Kγ-selective inhibitors.

Targets

PI3Kγ ^[1] (Cell-free assay)	PI3Kα ^[1] (Cell-free assay)	PI3Kβ ^[1] (Cell-free assay)	PI3Kδ ^[1] (Cell-free assay)
8 nM	60 nM	270 nM	300 nM

In vitro

AS-605240 is an ATP-competitive PI3Kγ inhibitor, with Ki values of 7.8 nM. AS-605240 is isoform-selective, for AS-605240 also inhibits PI3Kα, β, and δ, with IC50 of 60, 270, and 300 nM, respectively. AS-605240 inhibits C5a-mediated PKB phosphorylation with IC50 of 90 nM. In bone marrow-derived monocytes (BMDMs), AS-605240 (1 μM) blocks MCP-1- or CSF-1-induced PKB phosphorylation. ^[1] At SC-CA1 synapses in mice, AS-605240 (100 nM) eliminates NMDAR LTD, without affecting mGluR LTD, depotentiation, and LTP. ^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

RAW264.7 cells	M{joNmZ2dmO2aX;uJIF{e2G7				NHuz[YtKdmirYnn0bY9vKG:oIF3DVFEucW6mdXPl[EBkcGWvb4ThfIl{KGmwIH3veZNmKFKDV{K2OE44KGOnbHzzMEBKSzVyPUWuN\|Eh\|ryP	MmP1NVk6ODR7Mkm=

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot

p-AKT / AKT

25869207

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, AS-605240 (50 mg/kg) protects against αCII-IA symptom. In a mouse model of collagen-induced arthritis, AS-605240 (50 mg/kg) also suppresses joint inflammation and damage. ^[1] In an obesity-induced diabetes model (ob/ob mice), AS-605240 (10 mg/kg) lowers blood glucose levels, significantly improves both insulin sensitivity and glucose tolerance without affecting body weight. AS-605240 (30 mg/kg) displays more profound effects with slightly less weight gain. Moreover, AS-605240 reduces the abundance of ATMs and the circulating levels of MCP-1. ^[3]

Protocol (from reference)

Kinase Assay: ^[1]	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.
Cell Research: ^[1]	Cell lines: RAW264 macrophages Concentrations: 1 nM - 10 μM, dissolved in DMSO Incubation Time: 30 min Method: After a 3-hour starvation in serum-free medium, Cells are pretreated with AS-605240 or DMSO for 30 min and stimulated for 5 min with 50 nM of C5a. PKB phosphorylation is monitored using phosphorylated Ser473 Akt-specific antibody and standard ELISA protocols.
Animal Research: ^[1]	Animal Models: RANTES-induced mouse model of peritonitis (female Balb/C or C3H), αCII-induced mouse model of arthritis, and collagen-induced mouse model of arthritis (CIA) (male DBA/1) Dosages: 50 mg/kg Administration: Orally

References

Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 0.5% CMC+0.25% Tween 80 For best results, use promptly after mixing. Click to purchase: Tween 80	11 mg/mL

Chemical Information

Molecular Weight	257.27
Formula	C₁₂H₇N₃O₂S
CAS No.	648450-29-7
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1=CC2=NC=CN=C2C=C1C=C3C(=O)NC(=O)S3

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In vivo Formulation Calculator (Clear solution)

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Tech Support

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Handling Instructions

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