Wojtowicz-Praga S, Low J, Marshall J, Ness E, Dickson R, Barter J, Sale M, McCann P, Moore J, Cole A, Hawkins M J
Department of Medicine, Georgetown University, Lombardi Cancer Center, Washington, D.C., USA.
Invest New Drugs. 1996;14(2):193-202. doi: 10.1007/BF00210790.
Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. Batimastat inhibits at least 50% of MMP activity at concentrations less than or equal to 10 ng/ml in vitro. Batimastat retarded ascites accumulation and increased survival in mice with human ovarian tumor xenografts. Acute and long-term toxicological studies revealed no major toxicity in animals. Batimastat is poorly soluble and was administered intraperitoneally (i.p.) as a suspension. Previous studies in patients with malignant ascites have shown no major toxicities at doses as high as 1350 mg/m2.
基质金属蛋白酶（MMPs）对基底膜和细胞外基质的降解被认为是肿瘤侵袭、肿瘤诱导的血管生成和血管侵袭所必需的。一种合成异羟肟酸酯，batimastat（也称为BB-94），通过结合MMP活性位点中的锌离子来抑制MMPs。在体外，batimastat在浓度小于或等于10 ng/ml时可抑制至少50%的MMP活性。batimastat可延缓人卵巢肿瘤异种移植小鼠腹水的积聚并提高生存率。急性和长期毒理学研究表明该药物对动物无重大毒性。batimastat溶解性差，以悬浮液形式腹腔内给药（i.p.）。先前对恶性腹水患者的研究表明，在高达1350 mg/m2的剂量下无重大毒性。
