AS-604850

Catalog No.S2681 Batch:S268101

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Technical Data

Formula

C11H5F2NO4S
Molecular Weight 285.22 CAS No. 648449-76-7
Solubility (25°C)* In vitro DMSO 57 mg/mL (199.84 mM)
Ethanol 5 mg/mL (17.53 mM)
Water Insoluble
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.)

Preparing Stock Solutions

Biological Activity

Description AS-604850 is a selective, ATP-competitive PI3Kγ inhibitor with an IC50 of 250 nM, over 80-fold selectivity for PI3Kγ than PI3Kδ/β, and 18-fold more selective for PI3Kγ than PI3Kα.
Targets
PI3Kγ PI3Kα
0.25 μM 4.5 μM
In vitro AS-604850 is an ATP-competitive PI3Kγ inhibitor with Ki values of 0.18 μM. This compound is an isoform selective inhibitor of PI3Kγ with over 30-fold selectivity for PI3Kδ and β, and 18-fold selectivity over PI3Kα. (PI3Kα: IC50 = 4.5 μM, PI3Kγ and β: IC50 > 20μM) It is capable of inhibiting C5a-mediated PKB phosphorylation in RAW264 mouse macrophages with an IC50 of 10 μM. This chemical blocks MCP-1-mediated chemotaxis in Pik3cg+/+ monocytes in a concentration-dependent manner, with an IC50 of 21 mM, but doesn't affect chemotaxis in Pik3cg-/- cells, indicating that it acts through PI3Kγ. It diminishes glycochenodeoxycholate (GCDC) induced Akt-phosphorylation and apoptosis in rat hepatocytes. This compound diminishes bile salt-induced apoptosis in HepG2 Ntcp and Huh7-Ntcp cells. It causes a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to platelet-activating factor (PAF).
In Vivo AS-604850 reduces RANTES-induced peritoneal neutrophil recruitment with an ED50 of 42.4 mg/kg. In the thioglycollate-induced peritonitis model, oral administration of 10 mg/kg of this compound results in a 31% reduction of neutrophil recruitment.

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 this compound or DMSO. Kinase reaction is stopped by adding 250 g of Neomycin-coated Scintillation Proximity Assay (SPA) beads and preceded.
Cell Assay:[2]
  • Cell Lines

    HepG2 Ntcp and Huh7-Ntcp cells

  • Concentrations

    2.5 μM

  • Incubation Time

    2 - 4 hours

  • Method

    Hepatocyte cultures are treated with diluent (DMSO), 25 μM TLC, 250 μM TCDC, 50 μM GCDC, or 50 ng/ml Fas for 2-4 hours HepG2-Ntcp and Huh7-Ntcp cells are treated with DMSO, 20 μM TLC, 75 μM TCDC or GCDC, 200 μM etoposide or 200 ng/ml TNFa plus 28 ng/ml actinomycin D for 2-4 hours. The number of apoptotic cells is determined morphologically using fluorescent staining and expressed as % of cells. Apoptosis is confirmed in human cell lines by determination of caspase-3/-7 activity and in rat hepatocytes by detection of the 17 kDa proteolytic cleavage fragment of caspase-3 by immunoblotting; equal protein loading is monitored by immunoblotting for actin.
Animal Study:[1]
  • Animal Models

    RANTES (0.5 mg/kg in 200 ml saline) or thioglycollate (40 ml/kg) are intraperitoneally injected to C3H mice to induce peritonitis mouse models

  • Dosages

    0, 1, 3, 10 or 30 mg/kg for RANTES, 10 mg/kg for thioglycollate

  • Administration

    Oral administration 30 or 15 minutes before injection of RANTES or thioglycollate

References

  • https://pubmed.ncbi.nlm.nih.gov/16127437/
  • https://pubmed.ncbi.nlm.nih.gov/20675006/
  • https://pubmed.ncbi.nlm.nih.gov/20685403/

Customer Product Validation

Representative blots of activated Rac1 and total Rac1 in response to high glucose shown in cells treated overnight with either DMSO or AS604850 (1 umol/liter).

Data from [ J Biol Chem , 2014 , 289(46), 32109-20 ]

<p>After starved in serum-free medium for 24h,A549 cells incubated with the indicated concentrations of AS-604850 for 3h,followed by 20-minute stimolation of 100ng/ml EGF.</p>

, , Dr. Zhang of Tianjin Medical University

Numbers of AID on-target (Igh and Igk loci) and off-target hot spots from WT and AID−/− B cells. Data pooled from at least n = 3 biological replicates

Data from [ , , Nature, 2017, 542(7642):489-493 ]

Sellecks AS-604850 Has Been Cited by 11 Publications

GLP-1 and GIP receptors signal through distinct β-arrestin 2-dependent pathways to regulate pancreatic β cell function [ Cell Rep, 2023, 10.1016/j.celrep.2023.113326] PubMed: 37897727
DOCK2 and phosphoinositide-3 kinase δ mediate two complementary signaling pathways for CXCR5-dependent B cell migration [ Front Immunol, 2022, 13:982383] PubMed: 36341455
Repressing MYC by targeting BET synergizes with selective inhibition of PI3Kα against B cell lymphoma [ Cancer Lett, 2021, S0304-3835(21)00532-2] PubMed: 34688842
Retromer Complex and PI3K Complex II-Related Genes Mediate the Yeast (Saccharomyces cerevisiae) Sodium Metabisulfite Resistance Response [ Cells, 2021, 10(12)3512] PubMed: 34944020
Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita [ Front Med (Lausanne), 2021, 8:713312] PubMed: 34557502
Mussel-inspired injectable hydrogel and its counterpart for actuating proliferation and neuronal differentiation of retinal progenitor cells [ Biomaterials, 2019, 194:57-72] PubMed: 30583149
Recruitment of Vps34 PI3K and enrichment of PI3P phosphoinositide in the viral replication compartment is crucial for replication of a positive-strand RNA virus [ PLoS Pathog, 2019, 15(1):e1007530] PubMed: 30625229
PI3Kβ links integrin activation and PI(3,4)P2 production during invadopodial maturation. [ Mol Biol Cell, 2019, 30(18):2367-2376] PubMed: 31318314
Phosphatidylinositol 3-kinase δ Blockade Increases Genomic Instability in B Cells [ Nature, 2017, 23;542(7642):489-493.] PubMed: 28199309
Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells. [Compagno M, et al. Nature, 2017, 542(7642):489-493] PubMed: 28199309

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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.