2. Academic Validation
  3. Correlation of antiangiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor

Correlation of antiangiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor

  • Cancer Res. 1999 Mar 15;59(6):1231-5.
R Maekawa 1,  H Maki,  H Yoshida,  K Hojo,  H Tanaka,  T Wada,  N Uchida,  Y Takeda,  H Kasai,  H Okamoto,  H Tsuzuki,  Y Kambayashi,  F Watanabe,  K Kawada,  K Toda,  M Ohtani,  K Sugita,  T Yoshioka
Affiliations

Affiliation

  • 1 Discovery Research Laboratories, Shionogi and Company, Ltd., Osaka, Japan.
PMID: 10096553
Abstract

The antiangiogenic activity and antitumor efficacy of a newly developed matrix metalloproteinase (MMP) inhibitor were examined. N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA) potently inhibits MMP-2, -9, and -14, but not MMP-1, -3, or -7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMPs tested. Daily oral administration of 200 mg/kg BPHA, but not (-)BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth, and liver metastasis. The growth inhibition activity of BPHA was 48% and 45% in a B16-BL6 melanoma and F2 hemangio-endothelioma model, respectively. BPHA also showed 42% inhibition of the liver metastasis of C-1H human colon carcinoma cells. These results indicate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP Inhibitor BPHA has therapeutic potential.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-114785
    MMP-2/MMP-9/MMP-14 Inhibitor
    MMP