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NPS-1034

CAS No. : 1221713-92-3

MCE 国际站：NPS-1034

产品活性：NPS-1034 是 AXL 和 MET 的双重抑制剂，其 IC₅₀ 值分别为 10.3 和 48 nM。

研究领域：Protein Tyrosine Kinase/RTK  |  Apoptosis

作用靶点：TAM Receptor  |  c-Met/HGFR  |  Apoptosis

In Vitro: NPS-1034 is a dual inhibitor of AXL and MET with IC₅₀s of 10.3 and 48 nM, respectively.The expression and activity of AXL is significantly increased in HCC827/ER cells, and NPS-1034 treatment effectively inhibits its tyrosine phosphorylation. NPS-1034 inhibits the viability of the MKN45 and SNU638 cell lines, which highly express the MET gene and p-MET (phosphorylated MET), with IC₅₀ values of 112.7 and 190.3 nmol, respectively. In contrast, NPS-1034 inhibits AGS, KATOIII, NCI-N87, MKN1, MKN28, and MKN74 cell viability with IC₅₀ values ranging from 1 μmol to more than 10 μmol. MET phosphorylation is dramatically decreased after treatment with NPS-1034 in the MKN45 cells, but not in the MKN28 cells. NPS-1034 inhibits hepatocyte growth factor (HGF)-stimulated MET autophosphorylation (Y1234/1235) in the AGS and MKN1 cell lines with IC₅₀ values of <10 and <50 nmol, respectively. HGF-induced MET phosphorylation is completely inhibited by 50 nmol NPS-1034.

In Vivo: NPS-1034 inhibits tumor proliferation, which highly expresses p-MET. NPS-1034 treatment induces a clear decrease in the vascularization of the tumors. The expression of alpha-smooth muscle actin (α-SMA) is decreased in the tumor sections of mice treated with NPS-1034. NPS-1034-treated mice show virtually no weight loss, indicating that NPS-1034 is generally well tolerated.

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