Development of a New Antiangiogenic Tumor Blocker SBD 1

新型抗血管生成肿瘤阻断剂 SBD 1 的开发

基本信息

批准号：
6479621
负责人：
KRYS BOJANOWSKI
金额：
$ 22.76万
依托单位：
SUNNY BIODISCOVERY, INC.
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-06-01 至 2003-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6479621
关键词：
angiogenesis inhibitors antineoplastics athymic mouse breast neoplasms clinical research drug design /synthesis /production drug screening /evaluation human tissue lung neoplasms molecular cloning neoplasm /cancer blood supply prostate neoplasms protein purification protein sequence protein structure function

项目摘要

Inhibition of tumor angiogenesis-the growth of new blood vessels towards the tumor mass-is a new and promising approach to anti-cancer therapy. The results of Phase I/II clinical trials completed so far with several angiogenesis inhibitors validate the concept of tumor angiogenesis as effective target for anti-cancer therapy. However, the same studies stress the need for novel, more potent angiogenesis inhibitors. We addressed this need by isolating the human urine a new protein (SBD.1), which specifically blocks the proliferation of capillary endothelial cells in vitro (ID50=15NG/ML), angiogenesis in chorioallentoic membrane assay, and two growth in vivo (Lewis Lung Carcinoma, T/C=0.04 at 20umum/kg/day), placing SBD.1 among the most potent known angiogenesis inhibitors. Sequencing of SBD/1 showed it is a novel protein and its mild proteolysis resulted in the generation of smaller peptides without losing the inhibitory activity. Here, we propose to a) clone and express SBD.1 in a recombinant system; b) isolate and sequence the activity SBD.1 fragments; c) test the purified SBD.1 on prostate, lung and breast carcinoma human xenografts in nude mice to further assess its anti-tumor activity This project will result in the cloning of a novel therapeutically-active protein, which may be an important endogenous regulator of angio- and tumorigenesis in humans. PROPOSED COMMERCIAL APPLICATIONS: The development of SBD.1 addresses a pressing need in the pharmaceutical industry for a new, better angiogenesis inhibitor. Currently targeting anti-cancer therapy, the use of SBD.1 might be later extended to the treatment of vascular pathologies, such as macular degeneration and certain cardiovascular diseases. Meanwhile, SBD.1 can also be commercialized as reagent for laboratory research on angiogenesis. Taken together, these applications represent a substantial potential market for SBD.1

抑制肿瘤血管生成（新血管向肿瘤块生长）是一种新的、有前途的抗癌治疗方法。迄今为止，针对多种血管生成抑制剂完成的 I/II 期临床试验结果验证了肿瘤血管生成作为抗癌治疗有效靶点的概念。然而，同样的研究强调需要新型、更有效的血管生成抑制剂。我们通过从人尿中分离出一种新蛋白 (SBD.1) 来满足这一需求，该蛋白特异性阻断体外毛细血管内皮细胞的增殖 (ID50=15NG/ML)、绒毛尿囊膜测定中的血管生成以及两种体内生长 (Lewis肺癌，T/C=0.04（20umum/kg/天），使 SBD.1 成为已知最有效的血管生成抑制剂之一。 SBD/1 的测序表明它是一种新型蛋白质，其温和的蛋白水解作用导致生成更小的肽而不会失去抑制活性。在这里，我们建议a)在重组系统中克隆并表达SBD.1； b) 分离并测序SBD.1活性片段； c) 在裸鼠的前列腺癌、肺癌和乳腺癌人类异种移植物上测试纯化的SBD.1，以进一步评估其抗肿瘤活性。该项目将克隆一种新型治疗活性蛋白，该蛋白可能是一种重要的内源性调节因子人类血管和肿瘤发生的研究。拟议的商业应用：SBD.1 的开发满足了制药行业对新型、更好的血管生成抑制剂的迫切需求。 SBD.1目前的目标是抗癌治疗，以后可能会扩展到血管病变的治疗，例如黄斑变性和某些心血管疾病。同时，SBD.1也可以作为血管生成实验室研究试剂进行商业化。总而言之，这些应用代表了 SBD 的巨大潜在市场。1