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NVP-ADW742 475488-23-4
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C28H31N5O |
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453.58 |
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Introduction
NVP-ADW742 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 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.
Products for scientific research use only
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.
Products for scientific research use only