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 - 新血管对肿瘤质量的生长 - 是一种新的抗癌治疗方法。到目前为止，I/II期临床试验的结果以几种血管生成抑制剂验证了肿瘤血管生成的概念是抗癌治疗的有效靶标。然而，相同的研究强调了对新型，更有效的血管生成抑制剂的需求。我们通过隔离人类尿液A新蛋白（SBD.1）来解决这种需求，该蛋白特异性地阻断了体外毛细血管内皮细胞的增殖（ID50 = 15ng/mL），绒毛膜甲状腺甲状腺膜膜分析中的血管生成，Vivo中的两种生长（Lewis lung Carcinoma in t/cg/cg/cg = 0.0.00.0.0.00.00.0.00.00.00.00.00.044 art/c = 0.0.044，最有效的已知血管生成抑制剂之一。 SBD/1的测序表明它是一种新颖的蛋白质，其轻度蛋白水解导致产生较小的肽而不会失去抑制活性。在这里，我们向重组系统中的a）克隆和表达SBD.1。 b）分离并测序活性SBD.1片段； c）在裸鼠中测试纯化的SBD.1对前列腺，肺和乳腺癌的人异种移植物，以进一步评估其抗肿瘤活性该项目将导致克隆新颖的治疗性蛋白质，这可能是人类血管疾病和肿瘤的重要内源性调节剂。拟议的商业应用：SBD.1的发展解决了制药行业对一种新的，更好的血管生成抑制剂的紧迫需求。目前针对抗癌疗法，使用SBD.1后来可能会扩展到血管病理的治疗，例如黄斑变性和某些心血管疾病。同时，SBD.1也可以作为用于血管生成的实验室研究的试剂将其商业化。综上所述，这些应用代表了SBD的巨大潜在市场。1