Home Protein Tyrosine Kinase IGF-1R inhibitor NVP-ADW742 For research use only.

NVP-ADW742

Synonyms: GSK 552602A, ADW742

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.

NVP-ADW742 Chemical Structure

NVP-ADW742 Chemical Structure

CAS No. 475488-23-4

Purity & Quality Control

NVP-ADW742 Related Products

Signaling Pathway

IGF-1R Signaling Pathways

IGF-1R Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf21 cells Function assay Inhibition of human IGF1R expressed in Sf21 cells by time-resolved fluorescence assay, IC50=0.078 μM 17689078
MiaPaCa2 cells Function assay Inhibition IGF1R phosphorylation in human MiaPaCa2 cells, IC50=0.323 μM 17689078
Click to View More Cell Line Experimental Data

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
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) or investigational (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, TRAIL/Apo2L, or PS-341. [1]
Kinase Assay 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 Research 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.
In Vivo
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. [1]
Animal Research 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

Chemical Information & Solubility

Molecular Weight 453.58 Formula

C28H31N5O
CAS No. 475488-23-4 SDF Download NVP-ADW742 SDF
Smiles C1CCN(C1)CC2CC(C2)N3C=C(C4=C(N=CN=C43)N)C5=CC(=CC=C5)OCC6=CC=CC=C6
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 22 mg/mL ( (48.5 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 20 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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