NVP-ADW742

Catalog No.S1088 Batch:S108803

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Technical Data

Formula

C28H31N5O
Molecular Weight 453.58 CAS No. 475488-23-4
Solubility (25°C)* In vitro DMSO 10 mg/mL (22.04 mM)
Ethanol 4 mg/mL (8.81 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
IGF-1R [1]
(cellular autophosphorylation assays)
0.17 μM
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    MM-1S, MM-1R, RPMI-8226/S, OPM-1, OCI-My5, SKMM2, KMS-12-BM, XG-1, L363, S6B45 cells and et al.

  • Concentrations

    Dissolved in DMSO, final concentrations ~ 10 μM

  • Incubation Time

    48 hours

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Male SCID/NOD mice injected i.v. with MM-1S-Luc+ human MM cells

  • Dosages

    10 mg/kg twice daily

  • Administration

    Injection i.p. or oral gavage

Customer Product Validation

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's NVP-ADW742 has been cited by 22 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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