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A Small Compound That Inhibits Tumor Necrosis Factor-Alpha-Induced Matrix metalloproteinase-9 Upregulation

A Small Compound That Inhibits Tumor Necrosis Factor-Alpha-Induced Matrix metalloproteinase-9 Upregulation

Ha Young Lee, Kyoung Sun Park, Mi-Kyoung Kim, Taehoon Lee, Sung Ho Ryu, Kyung Jin Woo, Taeg Kyu Kwon, Yoe-Sik Bae

Biochem Biophys Res Commun. 2005 Oct 21;336(2):716-22.

PMID: 16140265

Abstract:

Matrix metalloproteinase-9 (MMP-9) is critically involved in the tumor invasion and metastasis processes. Since TNF-alpha plays a crucial role in the regulation of MMP-9 expression, the development of molecules capable of modulating TNF-alpha-induced signaling is an issue of concern. We identified a novel synthetic compound that inhibits TNF-alpha-induced MMP-9 upregulation in the HT1080 human fibrosarcoma cell line. The active compound SM-7368 inhibited TNF-alpha-induced MMP-9 upregulation in a concentration-dependent manner and showed maximal activity at 10 microM. SM-7368 inhibited TNF-alpha-induced MMP-9 mRNA transcript accumulation and protein expression. We also found that SM-7368 strongly inhibits TNF-alpha-induced NF-kappaB activity but not AP-1 activity. Moreover, we found that SM-7368 strongly inhibits the TNF-alpha-induced invasion of HT1080 human fibrosarcoma cell line. Taken together, our results demonstrate that SM-7368 is a synthetic compound that inhibits TNF-alpha-induced MMP-9 expression, and thus SM-7368 should be useful for the development of chemotherapies targeting TNF-alpha-mediated tumor invasion and metastasis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP380623767	SM-7368		380623-76-7	Price

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