NVP-ADW742

製品コードS1088 バッチS108804

印刷

化学情報

Chemical Structure Synonyms GSK 552602A, ADW742 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C28H31N5O
分子量 453.58 CAS No. 475488-23-4
Solubility (25°C)* 体外 Ethanol 12 mg/mL (26.45 mM)
DMSO 10 mg/mL warmed with 50ºC water bath (22.04 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 NVP-ADW742 (GSK 552602A) is an IGF-1R inhibitor with IC50 of 0.17 μM, >16-fold more potent against IGF-1R than InsR; little activity to HER2, PDGFR, VEGFR-2, Bcr-Abl and c-Kit.
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. NVP-ADW742 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. NVP-ADW742 also abrogates the responsiveness of tumor cells to IL-6 in the presence of serum. In addition, NVP-ADW742 is active against MM cell lines with resistance to conventional (cytotoxic chemotherapy, dexamethasone) or investigational (thalidomide, CC-5013, TRAIL/Apo2L, PS-341) anticancer agents, as well as primary tumor cells from MM patients with multi-drug-resistant disease. NVP-ADW742 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 NVP-ADW742 (0.75 μM) sensitizes MM cells or prostate cancer cells to other anticancer agents such as doxorubicin, melphalan, dexamethasone, TRAIL/Apo2L, or PS-341. [1]
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 melphalan in the mice model of diffuse MM. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Cellular kinase activity assay
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 NVP-ADW742, 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 NVP-ADW742 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.
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

カスタマーフィードバック

Data from [Biochem Biophys Res Commun, 2013, 436(4), 740-5]

Data from [Data independently produced by , , BMC Cancer, 2016, 16:475]

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：

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
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
Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic䲧盋Ỵ盌 [ Oncol Rep, 2020, 44(6):2581-2594] PubMed: 33125153
Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay. [ Sci Rep, 2019, 9(1):10278] PubMed: 31311976

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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