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受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 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
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Synonyms | GSK 552602A, ADW742 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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| 化学式 | C28H31N5O |
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| 分子量 | 453.58 | CAS No. | 475488-23-4 | ||||
| Solubility (25°C)* | 体外 | DMSO (warmed with 50ºC water bath) | 10 mg/mL (22.04 mM) | ||||
| Ethanol | 3 mg/mL (6.61 mM) | ||||||
| Water | Insoluble | ||||||
| 体内 （毎回新しく調製した物を用意してください） |
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | NVP-ADW742（GSK 552602A）は、IC50が0.17 μMのIGF-1R阻害剤であり、InsRよりもIGF-1Rに対して16倍以上強力です。HER2、PDGFR、VEGFR-2、Bcr-Abl、c-Kitに対する活性はほとんどありません。 |
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| in vitro | NVP-ADW742 exhibits a 6-fold greater selectivity for IGF-1R versus InsR with IC50 of 2.8 μM; minimal inhibitory activity against c-Kit, HER1, PDGFR, VEGFR2, or Bcr-Abl p210 with IC50 greater than 5 μM. This compound significantly inhibits the serum-stimulated cell proliferation in a variety of tumor cell lines in dose-dependent manner, with IC50 values of 0.1-0.5 μM for the multiple myeloma (MM) cell lines, and the antitumor effects on MM cells can not be overcome by the co-culture with BMSCs. It also abrogates the responsiveness of tumor cells to IL-6 in the presence of serum. In addition, this chemical is active against MM cell lines with resistance to conventional (cytotoxic chemotherapy) or investigational (CC-5013, TRAIL/Apo2L, PS-341) anticancer agents, as well as primary tumor cells from MM patients with multi-drug-resistant disease. This compound decreases the production of VEGF by tumor cells and bone marrow stromal cells, and suppresses the IGF-1-induced secretion of VEGF by various tumor types such as thyroid cancer cells or MM cells. IGF-1R inhibition by this compound (0.75 μM) sensitizes MM cells or prostate cancer cells to other anticancer agents such as doxorubicin, TRAIL/Apo2L, or PS-341. |
| in vivo | Administration of NVP-ADW742 at 10 mg/kg twice daily significantly inhibits tumor growth, prolongs survival, and enhances the antitumor effect of cytotoxic chemotherapy in the mice model of diffuse MM. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Cellular kinase activity assay | |
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| The IC50 value for the effect of NVP-ADW742 on the autophosphorylation of IGF-1R is determined at the cellular level in the presence of increasing concentrations of this compound, using 96-well “Capture ELISAs” assays. Briefly, NWT-21 cells are seeded into 96-well tissue culture plates in complete growth medium and grown to 70-80% confluency, and are then starved for 24 hours in 0.5% FCS medium. Subsequently, cells are incubated for 90 minutes in the presence of this inhibitor followed by the stimulation with of IGF-I (10 ng/mL) for 10 minutes at 37 °C. Subsequently, the cells are washed twice with ice-cold PBS and lysed at 4 °C with 50 μL/well RIPA-buffer (50 mM Tris-HCl, pH 7.2, 120 mM NaCl, 1 mM EDTA, 6 mM EGTA, 1% NP-40, 20 mM NaF, 1 mM benzamidine, 15 mM sodium pyrophosphate, 1 mM PMSF and 0.5 mM Na3VO4). The lysates from each experiment are then transferred to black ELISA plates precoated with capture antibodies specific for IGF-1R. After capture by the antibodies, lysates are mixed with 40 μL of an alkaline phosphatase (AP) labelled anti-phosphotyrosine Ab (PY20(AP) diluted to 0.2 μg/mL in RIPA buffer, and incubated overnight at 4 °C. After washing (PBST) and incubation for 45 minutes at RT with the luminescent AP-substrate CDPStar RTU with Emerald II (90 μL/well), luminescence is measured using a Packard Top Count Scintillation Counter. | ||
| 細胞アッセイ | 細胞株 | MM-1S, MM-1R, RPMI-8226/S, OPM-1, OCI-My5, SKMM2, KMS-12-BM, XG-1, L363, S6B45 cells and et al. |
| 濃度 | Dissolved in DMSO, final concentrations ~ 10 μM | |
| 反応時間 | 48 hours | |
| 実験の流れ | Cells are exposed to various concentrations of NVP-ADW742 for 48 hours in the presence or absence of serum. Cell survival is examined using MTT assay. |
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| 動物実験 | 動物モデル | Male SCID/NOD mice injected i.v. with MM-1S-Luc+ human MM cells |
| 投薬量 | 10 mg/kg twice daily | |
| 投与方法 | Injection i.p. or oral gavage | |
参考
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カスタマーフィードバック
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Data from [Biochem Biophys Res Commun, 2013, 436(4), 740-5]
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Data from [Data independently produced by , , BMC Cancer, 2016, 16:475]
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Data from [Data independently produced by , , Biochim Biophys Acta, 2018, 1865(6):920-931]
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：
| A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] | PubMed: 40147445 |
| Clcf1/Crlf1a-mediated signaling is neuroprotective and required for Müller glia proliferation in the light-damaged zebrafish retina [ Front Cell Dev Biol, 2023, 11:1142586] | PubMed: 36846595 |
| High-Content and High-Throughput Clonogenic Survival Assay Using Fluorescence Barcoding [ Cancers -Basel), 2023, 15(19)4772] | PubMed: 37835466 |
| Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] | PubMed: 35868306 |
| Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7] | PubMed: 35332332 |
| Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma [ Head Neck, 2022, 44(5):1192-1205] | PubMed: 35224804 |
| IGF-1R depletion sensitizes colon cancer cell lines to radiotherapy [ Cancer Biomark, 2021, 10.3233/CBM-210016] | PubMed: 34092618 |
| IGF1R as a pharmacological target in allergic asthma and cancer-promoting factor in the lung tumor microenvironment [ University of La Rioja, Publications Service, 2021, ] | PubMed: None |
| Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation. [ Int J Mol Sci, 2020, 21(3)] | PubMed: 32033461 |
| Identification of a cross-talk between EGFR and Wnt/beta-catenin signaling pathways in HepG2 liver cancer cells [ Cell Signal, 2020, S0898-6568(20)30362-4] | PubMed: 33340661 |
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。