受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C12H7N3O2S |
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分子量 | 257.27 | CAS No. | 648450-29-7 | |
Solubility (25°C)* | 体外 | DMSO | 1 mg/mL (3.88 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. |
製品説明 | 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. |
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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] |
特徴 | The most potent member of a new class of PI3Kγ-selective inhibitors. |
キナーゼアッセイ | In vitro PI3K lipid kinase assay | |
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(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. | ||
細胞アッセイ | 細胞株 | RAW264 macrophages |
濃度 | 1 nM - 10 μM, dissolved in DMSO | |
反応時間 | 30 min | |
実験の流れ | 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. |
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動物実験 | 動物モデル | 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) |
投薬量 | 50 mg/kg | |
投与方法 | Orally |
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, , 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]
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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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