Maki H, Maekawa R, Yoshida H, Hojo K, Uchida N, Wada T, Tanaka H, Takeda Y, Matsumoto M, Yamada H, Nishitani Y, Shono K, Kasai H, Sato S, Okamoto H, Hayashi R, Tamura Y, Tsuzuki H, Watanabe F, Sugita K, Yoshioka T
Research Laboratories, Shionogi & Co., Ltd.
Gan To Kagaku Ryoho. 1999 Oct;26(11):1599-606.
We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (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 MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.
我们研究了一种新开发的基质金属蛋白酶（MMP）抑制剂BPHA（N-联苯磺酰-苯丙氨酸异羟肟酸）的抗血管生成和抗肿瘤功效。BPHA能有效抑制MMP-2、9和14，但对MMP-1、3或7无抑制作用。相比之下，BPHA的对映体（-）BPHA对所有测试的MMP均无活性。在小鼠中每日口服BPHA可有效抑制肿瘤诱导的血管生成、原发性肿瘤生长和肝转移，而（-）BPHA则无此作用。这些结果表明，选择性MMP抑制与抗血管生成和抗肿瘤功效相关，且选择性MMP抑制剂BPHA具有治疗潜力，无血液毒性作用或体重减轻。
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