Linsitinib (OSI-906)

製品コードS1091 バッチS109109

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H23N5O
分子量 421.49 CAS No. 867160-71-2
Solubility (25°C)* 体外 DMSO 84 mg/mL (199.29 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (11.86mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Linsitinib (OSI-906) is a selective inhibitor of IGF-1R with IC50 of 35 nM in cell-free assays; modestly potent to InsR with IC50 of 75 nM, and no activity towards Abl, ALK, BTK, EGFR, FGFR1/2, PKA etc. Phase 3.
in vitro Linsitinib (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. It enables an intermediate conformation of the target protein through interactions with the C-helix and displays favorable metabolic stability in liver microsomes. This compound fully inhibits both IR and IGF-1R phosphorylation at a concentration of 1 μM and 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 Linsitinib (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. Its administration induces different elimination half-lives in dog, rat and mice, which are 1.18 hours, 2.64 hours and 2.14 hours, respectively. When administered at different single doses once-daily in female Sprague-Dawley rats and female CD-1 mice, it reveals that Vmax is not dose-proportional to its dose. This compound elevates blood glucose levels at a dose of 25 mg/kg after 12 days of administration. At a single dose of 75 mg/kg in an IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model, it achieves maximal inhibition of IGF-1R phosphorylation (80%) between 4 and 24 hours with plasma drug concentrations of 26.6-4.77 μM. [1] When administered as a single dose of 60 mg/kg in NCI-H292 xenograft mice, it inhibits uptake of glucose at 2, 4, and 24 hours post-treatment in vivo. It also inhibits the growth of tumors in an NCI-H292 xenograft mouse model. [2]

プロトコル(参考用のみ)

キナーゼアッセイ 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. At a concentration of 1 µM, this compound is profiled versus a panel of kinases using the ProfilerProTM Kinase Selectivity Assay Kit.
細胞アッセイ 細胞株 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
反応時間 3 days
実験の流れ 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 Linsitinib (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 this compound by the cellular density of control cells treated with vehicle (DMSO) only.
動物実験 動物モデル IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model
投薬量 25 mg / kg and 75 mg / kg
投与方法 Orally administrated at once-daily oral dose for 14 days

参考

  • https://pubmed.ncbi.nlm.nih.gov/21425998/
  • https://pubmed.ncbi.nlm.nih.gov/21257723/

カスタマーフィードバック

Data from [Cancer Res, 2013, 73, 834-843]

Data from [Cancer Res, 2011, 71, 6773-84]

,

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：

Placenta-derived factors contribute to human iPSC-liver organoid growth [ Nat Commun, 2025, 16(1):2493] PubMed: 40082402
Enhanced regenerative and developmental potential of embryonal and stem cell-derived platelets compared to adult platelets [ Cell Rep Med, 2025, 6(8):102297] PubMed: 40795844
Imeglimin suppresses glucagon secretion and induces a loss of α cell identity [ Cell Rep Med, 2025, 6(8):102254] PubMed: 40713970
PI3K-dependent GAB1/Erk phosphorylation renders head and neck squamous cell carcinoma sensitive to PI3Kα inhibitors [ Cell Death Dis, 2025, 16(1):457] PubMed: 40533463
Linsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human Thyrocytes In Vitro and In Vivo in Mice [ Thyroid, 2025, 35(2):216-224] PubMed: 39718934
Heparan sulfate fine-tuned interleukin-1 (IL-1) signaling inhibits insulin secretion of grafted pancreatic islets [ Sci Adv, 2025, 11(32):eady8566] PubMed: 40779638
Hypoxia-induced histone methylation and NF-κB activation in pancreas cancer fibroblasts promote EMT-supportive growth factor secretion [ bioRxiv, 2025, 2025.01.30.635486] PubMed: 39974981
Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2 [ Nat Commun, 2024, 15(1):6525] PubMed: 39117630
Caloric restriction leads to druggable LSD1-dependent cancer stem cells expansion [ Nat Commun, 2024, 15(1):828] PubMed: 38280853
Acinar-ductal cell rearrangement drives branching morphogenesis of the murine pancreas in an IGF/PI3K-dependent manner [ Dev Cell, 2024, 59(3):326-338.e5] PubMed: 38237591

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。