AS-605240

Catalog No.S1410 Batch:S141002

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Technical Data

Formula

C12H7N3O2S
Molecular Weight 257.27 CAS No. 648450-29-7
Solubility (25°C)* In vitro DMSO 0.4 mg/mL (1.55 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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

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 Assay:

[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 Study:

[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

Customer Product Validation

, , Dr. Zhang of Tianjin Medical University

, , Saraswati Sukumar of Johns Hopkins University School of Medicine

Data from [Data independently produced by , , Oncol Lett, 2018, 15(2):2105-2110]

Selleck's AS-605240 has been cited by 35 publications

Therapeutic potential of anti-PIK3CG treatment for multiple myeloma via inhibiting c-Myc pathway [ Heliyon, 2024, 10(1):e23165] PubMed: 38163179
Alcam-a and Pdgfr-α are essential for the development of sclerotome-derived stromal cells that support hematopoiesis [ Nat Commun, 2023, 14(1):1171] PubMed: 36859431
Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia [ Cell Rep, 2022, 41(6):111614] PubMed: 36351402
Connectivity Mapping Using a Novel sv2a Loss-of-Function Zebrafish Epilepsy Model as a Powerful Strategy for Anti-epileptic Drug Discovery [ Front Mol Neurosci, 2022, 15:881933] PubMed: 35686059
Grape-Seed-Derived Procyanidin Attenuates Chemotherapy-Induced Cognitive Impairment by Suppressing MMP-9 Activity and Related Blood-Brain-Barrier Damage [ Brain Sci, 2022, 12(5)571] PubMed: 35624958
A PI3Kγ signal regulates macrophage recruitment to injured tissue for regenerative cell survival [ Dev Growth Differ, 2022, 64(8):433-445] PubMed: 36101496
Oxytocin signalling in dendritic cells regulates immune tolerance in the intestine and alleviates DSS-induced colitis [ Clin Sci (Lond), 2021, 135(4):597-611] PubMed: 33564880
BTK and PI3K Inhibitors Reveal Synergistic Inhibitory Anti-Tumoral Effects in Canine Diffuse Large B-Cell Lymphoma Cells [ Int J Mol Sci, 2021, 22(23)12673] PubMed: 34884478
Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling [ Front Pharmacol, 2021, 12:743837] PubMed: 34512367
Distinct roles of PI3Kδ and PI3Kγ in a toluene diisocyanate-induced murine asthma model [ Toxicology, 2021, 454:152747] PubMed: 33711354

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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