MedKoo product information:

  ADW742

Description of ADW472 (NVP-ADW742): NVP-ADW742 is a novel small weight molecular inhibitor of IGF-IR with potential anticancer activity.  NVP-ADW742 could induce apoptosis in both HL-60 cell line and primary AML blasts. NVP-ADW742 also induced Akt dephosphorylation, which might subsequently induce p38 phosphorylation and decrease antiapoptotic protein Bcl-2 expression in HL-60 cells. 

Current developer:    Novartis Pharmaceuticals.

NVP-ADW742 is an IGF-I receptor (IGF-IR) kinase inhibitor, which has in vitro activity against tumors. NVP-ADW742 was found to inhibit IGF-IR-mediated proliferation with an IC50 of 11.12 µmol/l. The PCR array data suggested that 14 genes were down-regulated at the mRNA level after NVP-ADW742 treatment. Western blot analysis suggested that NVP-ADW742 induced early suppression of Akt, P38 and GSK-3β phosphorylation, as well as a decrease in the intracellular levels of PI3K, Akt, P38, GSK-3β and Bcl-2. Combined with NVP-ADW742 (2 µmol/l), IC50 of Daoy to temozolomide was decreased from 452.12 to 256.81 µmol/l. Cell apoptosis was enhanced from 16.18±2.47% to 23.20 ± 2.80%. G phase arrest was also found in both the temozolomide alone group and the temozolomide combined with NVP-ADW742 group. NVP-ADW742 inhibited the activation of PI3K, Akt, P38 and GSK-3β caused by temozolomide. NVP-ADW742 enhanced the chemosensitivity of Daoy to temozolomide in vitro, as a potent anti-tumor agent highly selective against IGF-IR. (source: Oncol Rep. 2011 Jun;25(6):1565-71. doi: 10.3892/or.2011.1233. Epub 2011 Mar 23.).

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2: Zhou H, Rao J, Lin J, Yin B, Sheng H, Lin F, Zhang N, Yang L. The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy. Oncol Rep. 2011 Jun;25(6):1565-71. doi: 10.3892/or.2011.1233. Epub 2011 Mar 23. PubMed PMID: 21455580.

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