[Antiangiogenic and antitumor effect of BPHA, an orally-active matrix metalloproteinase inhibitor, in in vivo murine and human tumor model].
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.
Maki
H
H
Research Laboratories, Shionogi & Co., Ltd.
Maekawa
R
R
Yoshida
H
H
Hojo
K
K
Uchida
N
N
Wada
T
T
Tanaka
H
H
Takeda
Y
Y
Matsumoto
M
M
Yamada
H
H
Nishitani
Y
Y
Shono
K
K
Kasai
H
H
Sato
S
S
Okamoto
H
H
Hayashi
R
R
Tamura
Y
Y
Tsuzuki
H
H
Watanabe
F
F
Sugita
K
K
Yoshioka
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; C400001:N-biphenylsulfonylphenylalanine hydroxamic acid