AS-252424

Catalog No.S2671 Batch:S267101

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Technical Data

Formula

C14H8FNO4S
Molecular Weight 305.28 CAS No. 900515-16-4
Solubility (25°C)* In vitro DMSO 61 mg/mL (199.81 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-252424 is a novel, potent PI3Kγ inhibitor with IC50 of 30 nM in a cell-free assay with 30-fold selectivity for PI3Kγ than PI3Kα, and low inhibitory activity towards PI3Kδ/β.
Targets
Casein Kinase 2 [1]
(Cell-free assay)		 PI3Kγ [1]
(Cell-free assay)		 PI3Kα [1]
(Cell-free assay)
20 nM 33 nM 935 nM
In vitro AS-252424 is a furan-2-ylmethylene thiazolidinedione as a selective ATP-competitive PI3Kγ inhibitor with IC50 with 33 nM. AS-252424 shows reduced potency on PI3Kα with an IC50 with 935 nM. When screening against 80 different Ser/Thr and Tyr kinases, AS-252424 doesn't show significant inhibit towards any of them at 10 μM except for CK2. AS-252424 inhibits C5a-mediated PKB/Akt phosphorylation in a concentration- dependent manner with submicromolar or low-micromolar IC50 value. AS-252424 inhibits MCP-1-mediated chemotaxis in wild-type primary monocytes in a concentration-dependent manner with an IC50 value of 52 μM, as well as in the monocytic cell line THP-1 with an IC50 value of 53 μM. [1] AS252424 specifically blocks proliferation in the pancreatic cancer cell lines HPAF and Capan1, as assessed by cell counting. [2] A recent research indicates 100 nM of AS-252424 significantly reduces [Ca2+]i, ICa and Ca2+ transients in HL-1 cardiomyocytes. [3]
In vivo Oral administration of AS-252424 at 10 mg/kg results in moderate reduction of neutrophil recruitment (35%), almost matching the result observed in PI3Kγ-deficient mice. [1]

Protocol (from reference)

Kinase Assay:[1]
  • In vitro PI3Kγ Kinase Assay

    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[33]ATP, final concentrations) and lipid vesicles containing 18 M PtdIns and 250 M of PtdSer (final concentrations), in the presence of AS-252424 or DMSO. Kinase reaction is stopped by adding 250 g of Neomycin-coated Scintillation Proximity Assay (SPA) beads and preceded.
Cell Assay:[1]
  • Cell lines

    Raw-264 macrophage

  • Concentrations

    0.01 nM to 0.1 μM

  • Incubation Time

    5 minutes

  • Method

    After 3 hours of starvation in serum-free medium, Raw-264 macrophages are pretreated with AS-252424 or DMSO for 30 minutes and stimulated for 5 minutes with 50 nM C5a. PKB/Akt phosphorylation is monitored using phospho-Ser-473 Akt specific antibody and standard ELISA protocols.
Animal Study:[1]
  • Animal Models

    Intraperitoneally injecting female C3H mice with thioglycollate (40 ml/kg) to induced a peritonitis mouse model

  • Dosages

    10 mg/kg

  • Administration

    Oral administration 15 minutes before injection of thioglycollate

Customer Product Validation

Data from [Data independently produced by Inflammation, 2014, 37(4), 1254-60]

, , Dr. Zhang of Tianjin Medical University

Data from [Data independently produced by , , Inflammation, 2017, 40(2):435-441]

Selleck's AS-252424 has been cited by 21 publications

Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development [ Int J Mol Sci, 2022, 23-1810600] PubMed: 36142542
Distinct roles of PI3Kδ and PI3Kγ in a toluene diisocyanate-induced murine asthma model [ Toxicology, 2021, 454:152747] PubMed: 33711354
Soluble Epoxide Hydrolase Inhibitors Regulate Ischemic Arrhythmia by Targeting MicroRNA-1 [ Front Physiol, 2021, 12:717119] PubMed: 34646152
Idelalisib Rescues Natural Killer Cells from Monocyte-Induced Immunosuppression by Inhibiting NOX2-Derived Reactive Oxygen Species [ Cancer Immunol Res, 2020, 8(12):1532-1541] PubMed: 32967913
Frailty is associated with neutrophil dysfunction which is correctable with phosphoinositol-3-kinase inhibitors [ J Gerontol A Biol Sci Med Sci, 2020, glaa216] PubMed: 32877922
Targeting effector pathways in RAC1P29S-driven malignant melanoma. [ Small GTPases, 2020, 10.1080/21541248] PubMed: 32043900
Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway [ Aging (Albany NY), 2019, 11(11):3768-3784] PubMed: 31182679
Critical roles for the phosphatidylinositide 3-kinase isoforms p110β and p110γ in thrombopoietin-mediated priming of platelet function [ Sci Rep, 2019, 9(1):1468] PubMed: 30728366
Role of PI3K/Akt and MEK/ERK Signalling in cAMP/Epac-Mediated Endothelial Barrier Stabilisation. [ Front Physiol, 2019, 10:1387] PubMed: 31787905
PI3Ka-Akt1-mediated Prdm4 induction in adipose tissue increases energy expenditure, inhibits weight gain, and improves insulin resistance in diet-induced obese mice [ Cell Death Dis, 2018, 9(9):876] PubMed: 30158592

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.