|
受注：045-509-1970 |
技術サポート：[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
|
Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C22H16F3N3O2S |
|||
| 分子量 | 443.44 | CAS No. | 728033-96-3 | |
| Solubility (25°C)* | 体外 | DMSO | 89 mg/mL (200.7 mM) | |
| Ethanol | 3 mg/mL (6.76 mM) | |||
| Water | 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. |
||||
溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | OSI-930 is a potent inhibitor of Kit (c-Kit), KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl. Phase 1. |
|---|---|
| in vitro | OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. Moreover, OSI-930 also induces apoptosis in HMC-1 cell line with EC50 of 34 nM. [1] A recent study shows that OSI-930 inactivates purified, recombinant cytochrome P450 (P450) 3A4 with a Ki of 24 μM in a time- and concentration-dependent mode. [2] |
| in vivo | OSI-930, administrated at the maximally efficacious dose of 200 mg/kg by oral gavage, exhibits potent antitumor activity in a broad range of preclinical xenograft models including HMC-1, NCI-SNU-5, COLO-205 and U251 xenograft models. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Protein kinase assays | |
|---|---|---|
| Protein kinase assays are either done in-house by ELISA-based assay methods (Kit, KDR, PDGFRα, and PDGFRβ) or by a radiometric method. In-house ELISA assays used poly(Glu:Tyr) as the substrate bound to the surface of 96-well assay plates; phosphorylation is then detected using an antiphosphotyrosine antibody conjugated to HRP. The bound antibody is then quantitated using ABTS as the peroxidase substrate by measuring the absorbance at 405/490 nm. All assays uses purified recombinant kinase catalytic domains that are either expressed in insect cells or in bacteria. The Kit and EGFR protein used for in-house assays are prepared internally; other enzymes are obtained. Recombinant Kit protein is expressed as an NH2-terminal glutathione S-transferase fusion protein in insect cells and is initially purified as a nonphosphorylated (nonactivated) enzyme with a relatively high Km for ATP (400 μM). In some assays, an activated (tyrosine phosphorylated) form of the enzyme is prepared by incubation with 1 mM ATP for 1 hour at 30 °C. The phosphorylated protein is then passed through a desalting column to remove the majority of the ATP and stored at −80 °C in buffer containing 50% glycerol. The resultant preparation has a considerably higher specific activity and a lower Km for ATP (25 μM) than the initial nonphosphorylated preparation. The inhibition of Kit autophosphorylation by OSI-930 is assayed by incubation of the nonphosphorylated enzyme at 30 °C in the presence of 200 μM ATP and various concentrations of OSI-930. The reaction is stopped by removal of aliquots into SDS-PAGE sample buffer followed by heating to 100 °C for 5 minutes. The degree of phosphorylation of Kit is then determined by immunoblotting for both total Kit and phosphorylated Kit. | ||
| 細胞アッセイ | 細胞株 | HMC-1 and COLO-205 |
| 濃度 | 0--1 μM | |
| 反応時間 | 48 hours | |
| 実験の流れ | For assays of cell proliferation and apoptosis, cells are seeded into 96-well plates and incubated for 2 to 3 days in the presence of OSI-930 at various concentrations. Inhibition of cell growth is determined by luminescent quantitation of the intracellular ATP content using CellTiterGlo. Induction of caspase-dependent apoptosis by OSI-930 is quantitated by an enzymatic caspase 3/7 assay. Inhibition of angiogenesis by OSI-930 is monitored using the rat aortic ring endothelial sprout outgrowth assay. Sections of aorta are prepared from CO2-euthanized male rats and cultured in vitro in a collagen matrix in the presence or absence of OSI-930. The collagen matrix is prepared from type 1 rat tail collagen solubilized in 0.1% acetic acid at 3 mg/mL, which is combined with 0.125 volume collagen buffer (0.05 N NaOH, 200 mM HEPES, 260 mM NaHCO3), 0.125 volume of medium 199, 0.0125 volume of 1 M NaOH, and 1% GlutaMax. Aortic rings are embedded in 0.4 mL of this matrix in six-well plates, to which 0.5 mL endothelial basal medium and the appropriate amount of OSI-930 is added; the rings are then incubated for 10 days and the resultant angiogenic sprout outgrowth is digitally quantitated from images by measurement of the sprout-containing area within a series of concentric rings around the aortic tissue area. | |
| 動物実験 | 動物モデル | HMC-1, NCI-SNU-5, COLO-205 and U251 cells are injected s.c. into the right flank of CD1 nu/nu mice. |
| 投薬量 | ≤200 mg/kg | |
| 投与方法 | Administered via p.o. | |
参考
|
カスタマーフィードバック
-
Data from [Data independently produced by BMC Microbiol, 2013, 13, 249]
-
,
-
, , Dr. Yong-Weon Yi from Georgetown University Medical Center
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors. [ Cell Rep, 2019, 28(9):2331-2344] | PubMed: 31461650 |
| TLR7/8-agonist-loaded Nanoparticles Promote the Polarization of Tumour-Associated Macrophages to Enhance Cancer Immunotherapy [ Nat Biomed Eng, 2018, 2(8):578-588] | PubMed: 31015631 |
| Targeting a cell state common to triple-negative breast cancers [Muellner MK, et al. Mol Syst Biol, 2015, 11(1):789] | PubMed: 25699542 |
| Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative breast cancer cells through downregulation of ribosomal protein S6 [ Int J Oncol, 2015, 47(1):122-32] | PubMed: 25955731 |
| Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative breast cancer cells through downregulation of ribosomal protein S6. [Yi YW, et al. Int J Oncol, 2015, 47(1):122-32] | PubMed: 25955731 |
| c-KIT signaling is targeted by pathogenic Yersinia to suppress the host immune response. [Micheva-Viteva SN, et al. BMC Microbiol, 2013, 13(1):249] | PubMed: 24206648 |
| OSI-930 analogues as novel reversal agents for ABCG2-mediated multidrug resistance. [Kuang Y, et al. Biochem Pharmacol, 2012, 84(6):766-74] | PubMed: 22750060 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。