OSI-906 (Linsitinib)

OSI-906(Linsitinib)は、IGF-IRとIrの選択的な阻害剤で、IC50 がそれぞれ 35 nM と 75 nMです。

目録号S1091
5 5 3レビュー 8製品表彰状
価格 在庫  
USD 214 In stock
USD 239 In stock
USD 340 In stock
USD 907 In stock
USD 2104 In stock

OSI-906 (Linsitinib) 化学構造
分子量: 421.49

品質と確認

カスタマーレビュー(3)

Quality Control & MSDS

製品情報

  • Compare IGF-1R Inhibitors
    IGF-1R阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 OSI-906(Linsitinib)は、IGF-IRとIrの選択的な阻害剤で、IC50 がそれぞれ 35 nM と 75 nMです。
目標 IGF-1R InsR
IC50 35 nM 75 nM [1]
In vitro試験 OSI-906 inhibits IGF-1R autophosphorylation and activation of the downstream signaling proteins Akt, ERK1/2 and S6 kinase with IC50 of 0.028 to 0.13 μM. OSI-906 enables an intermediate conformation of the target protein through interactions with the C-helix. OSI-906 displays favorable metabolic stability in liver microsomes. OSI-906 fully inhibits both IR and IGF-1R phosphorylation at a concentration of 1 μM. OSI-906 inhibits proliferation of several tumor cell lines including non-small-cell lung cancer and colorectal cancer (CRC) tumor cell line with EC50 of 0.021 to 0.810 μM. [1]
In vivo試験 OSI-906 inhibits tumor growth in an IGF-1R-driven xenograft mouse model, with 100% TGI and 55% regression at a dose of 75 mg/kg and 60% TGI and no regression at a dose of 25 mg/kg. OSI-906 administration induces different elimination half-lives of itself in dog, rat and mice, the elimination half-lives are 1.18 hours, 2.64 hours and 2.14 hours, respectively. OSI-906 administration at different single dose once-daily in femal Sprague-Dawley rat and femal CD-1 mouse reveal that the Vmax is not dose-proportional to OSI-906 dose. OSI-906 elevates the blood glucose levels at a dose of 25 mg/kg after 12 days administration. OSI-906 administration at a single dose of 75 mg/kg in IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model achieve maximal inhibition of IGF-1R phosphorylation (80%) between 4 and 24 hours with plasma drug concentrations of 26.6-4.77 μM. [1] OSI-906 administered as a single dose of at 60 mg/kg in NCI-H292 xenografts mice inhibits uptake of glucose at 2, 4, and 24 hours post-treatment in vivo. OSI-906 inhibits the growth of tumors in NCI-H292 xenograft mouse model. [2]
臨床試験 OSI-906 is currently under a Phase III clinical trial in adrenocortical carcinoma (ACC).
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ: [1]

Protein kinase biochemical assays Protein kinase assays are either performed in-house by ELISA-based assay methods (IGF-1R, IR, EGFR and KDR) or at Upstate Inc. by a radiometric method with ATP at 100 µM concentration. In-house ELISA assays use poly(Glu:Tyr) as the substrate bound to the surface of 96-well assay plates and phosphorylation is detected using an antiphosphotyrosine antibody conjugated to horseradish peroxidase. The bound antibody is quantified using ABTS as the peroxidase substrate by measuring absorbance at 405 / 490 nm. All assays use purified recombinant kinase catalytic domains. Recombinant enzymes of human IGF-1R or EGFR are expressed as an NH2-terminal glutathione S-transferase fusion protein in insect cells and are purified in house. IC50 values are determined from the sigmoidal dose–response plot of percent inhibition versus log10 compound concentration. A minimum of three measurements, performed in duplicate, are carried out with in-house assays unless otherwise indicated. OSI-906 at a concentration of 1 µM is profiled versus a panel of kinases using the ProfilerProTM Kinase Selectivity Assay Kit.

細胞アッセイ: [1]

細胞系 MCF7, NCI-H292, Colo-205, HT29, H358, H1703, BxPC3, A673, SW620, DU4475, HepG2 and Hepa-1, RKO 3T3/hulGF-IR and H292 cells
濃度 0.02-0.8 μM
処理時間 3 days
方法 For assays of cell proliferation, cells are seeded into 96-well plates in appropriate media containing FCS 10% and incubated for 3 days in the presence of OSI-906 at various concentrations. Inhibition of cell growth is determined by luminescent quantitation of intracellular ATP content using CellTiterGlo. Data is presented as a fraction of maximal proliferation, calculated by dividing the cellular density in the presence of varying concentrations of OSI-906 by the cellular density of control cells treated with vehicle (DMSO) only.

動物実験: [1]

動物モデル IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model
製剤 25 mM tartaric acid
投薬量 25 mg / kg and 75 mg / kg
管理 Orally administrated at once-daily oral dose for 14 days
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
* 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.
1

参考

化学情報

Download OSI-906 (Linsitinib) SDF
分子量 421.49
化学式

C26H23N5O

CAS No. 867160-71-2
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 84 mg/mL (199 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, 30 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.
化学名 (1s,3s)-3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol

研究分野

カスタマーレビュー (3)


Click to enlarge
Rating
Source Cancer Res, 2011, 71(21), 6773-84. OSI-906 (Linsitinib) purchased from Selleck
Method [18 F]FDG –PET/ Western blot
Cell Lines MCF-7 cells/athymic mice
Concentrations 50 mg/kg/day
Incubation Time 6 weeks
Results mice without palpable tumors were randomized to treatment with vehicle or OSI-906. Six of 20 control mice (30%) developed tumors, whereas none of the 20 OSI-906–treated mice did (Fig. A). OSI-906 inhibited tumor growth compared with vehicle (Fig. B; P < 0.05). OSI-906–treated tumors exhibited markedly lower levels of phosphorylated IGF-IR, InsR, IRS-1, AKT, and S6 compared with vehicle controls (Fig. C). FDG uptake was significantly decreased 4 hours after a single dose of OSI-906 com-pared with baseline (Fig. D)

Click to enlarge
Rating
Source Cancer Res, 2013, 73(2), 834-843. OSI-906 (Linsitinib) purchased from Selleck
Method Cell proliferation and growth assays
Cell Lines PFR3 cells
Concentrations 1 μM
Incubation Time
Results The IC50 of PFR3 cells for PF299804 was more than 100 fold lower with the combination of OSI-90 than with PF00299804 alone.

Click to enlarge
Rating
Source OSI-906 (Linsitinib) purchased from Selleck
Method Flow cytometry/ Western Blotting
Cell Lines CLL B cells
Concentrations 1 µM
Incubation Time 24 h
Results three structurally unrelated IGF1R inhibi tors AG1024, Picropodophyllin (PPP) and linsitinib significantly reduced the cellular viability of primary CLL cells ( Figure A) and reduced levels of phosphorylated IGF1R and IRS-1 (Figure B,C). AG1024, which showed the strongest effect on viability, caused a dose-dependent decrease in the levels of phosphorylated Src, PI3K, Akt, MEK and ERK (Figure D).

製品表彰状 (8)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の問い合わせをするならば、メッセージを残してください。

* 必須

Related IGF-1R 阻害剤

  • CO-1686 (AVL-301)

    CO-1686 (AVL-301) is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively.

  • AZD9291

    AZD9291 is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR, respectively. Phase 3.

  • ASP3026

    ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM.

  • EMD 1214063

    EMD 1214063 は強力かつ選択的な c-Met 阻害剤で、IC50 が 6 nMです。

  • BMS-536924

    BMS-536924は、ATP競争的IGF-IRとIR阻害剤で、IC50 がそれぞれ 100 nM と 73 nMです。

  • NVP-AEW541

    NVP-AEW541は、IGF-IRとInsRの二重阻害剤で、IC50 がそれぞれ 86 nM と 140 nMです。

  • NVP-ADW742

    NVP-ADW742は、0.17のμMのIC50によるIGF1R阻害剤です。

  • GSK1904529A

    GSK1904529Aは選択性阻害剤、(IGF-IR) と (IR)を抑制する時、 IC50が それぞれ27 nM と 25 nMになる.

  • BMS-754807

    BMS-754807は、IGF1R/IR家族キナーゼの強力で可逆的な阻害剤で、 IGF-1RIRMetTrkATrkBを妨げ、IC50 がそれぞれ 1.8 nM、1.7 nM、5.6 nM、7.4 nM 、 4.1 nMです。

    Features:胰岛素样生长因子-1R/IR家族激酶的多重抑制剂

最近見られたアイテム

Tags: OSI-906 (Linsitinib)を買う | OSI-906 (Linsitinib)供給者 | OSI-906 (Linsitinib)を購入する | OSI-906 (Linsitinib)費用 | OSI-906 (Linsitinib)生産者 | オーダーOSI-906 (Linsitinib) | OSI-906 (Linsitinib)代理店
お問い合わせ