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NVP-ADW742 Europäischer Partner

Hersteller Selleckchem
Kategorie
Typ Inhibitors
Specific against other
Menge 50 mg
ArtNr S1088-50
CAS-Nr. 475488-23-4
eClass 6.1 30220300
eClass 9.0 32160605
Lieferbar
Administration
Injection i.p. or oral gavage
Animal Models
Male SCID/NOD mice injected i.v. with MM-1S-Luc+ human MM cells
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.
Chemical Name
5-(3-(benzyloxy)phenyl)-7-((1r, 3r)-3-(pyrrolidin-1-ylmethyl)cyclobutyl)-7H-pyrrolo[2, 3-d]pyrimidin-4-amine
Concentrations
Dissolved in DMSO, final concentrations ca. 10 uM
Description
NVP-ADW742 is an IGF-1R inhibitor with IC50 of 0.17 uM.
Dosages
10 mg/kg twice daily
Formulation
Formulated in 25 mM tartaric acid
IC50
0.17 uM [1], 0.17 uM [1], 0.17 uM [1], 0.17 uM [1], 0.17 uM [1], 0.17 uM [1]
In vitro
NVP-ADW742 exhibits a 6-fold greater selectivity for IGF-1R versus InsR with IC50 of 2.8 uM, minimal inhibitory activity against c-Kit, HER1, PDGFR, VEGFR2, or Bcr-Abl p210 with IC50 greater than 5 uM. 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 uM 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 uM) 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]
Incubation Time
48 hours
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 uL/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 aixed with 40 uL of an alkaline phosphatase (AP) labelled anti-phosphotyrosine Ab (PY20(AP) diluted to 0.2 ug/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 uL/well), luminescence is measured using a Packard Top Count Scintillation Counter.
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.
Molecular Weight (MW)
453, 58
Picture ChemicalStructure Description
NVP-ADW742 Chemical Structure
Solubility (25C)
DMSO 10 mg/mL, Water <1 mg/mL, Ethanol 3 mg/mL
Storage
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO

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Menge: 50 mg
Lieferbar: In stock
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Lieferung vsl. bis 11.04.2024 

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