Structure-Activity Relationship of CM101 Tumor antiangiogenic agent with its lect

描述（由申请人提供）：CM101是由B群链球菌发酵产生的靶向肿瘤血管生成、补体活化、免疫刺激的多糖生物。CM101结合毛细血管内皮受体HP59，引起炎症细胞因子级联反应，招募CD69+粒细胞破坏新生血管和周围肿瘤。本SBIR提案旨在确定CM101的结构-活性-关系（SAR），以确定血管生成特异性的hp59靶向机制，并建立最小活性分子结构（药效团）。CM101不像阿瓦斯汀及相关生物制剂和药物那样是血管生成抑制剂，但具有完全不同的作用机制，刺激对HP59+肿瘤新生血管的免疫攻击。CM101是一种很有前景的生物活性药物成分（API），用于癌症治疗，动物研究结果和1997年发表的人体I期安全性试验。CM101纯化和HP59受体的最新知识产权现在保护产品到2026-2028年。尽管CM101的技术很有前途，但由于以前的业务失败，CM101的开发中断了。通过建立药效团，确定与肿瘤毛细血管内皮凝集素受体HP59的生化结合相互作用（参见维基百科），我们将发现作用机理细节，物质知识产权的新组成，以及小型药物管道开发的潜力，以刺激投资者和主要制药公司支持计划的I/II期临床试验。综上所述，B组链球菌毒素（GBS-Toxin） CM101是一种270Kda的多糖，可靶向结合肿瘤细胞内皮细胞表面凝集素HP59，因此是一种高度特异性的肿瘤血管靶向生物

DESCRIPTION (provided by applicant): CM101 is a polysaccharide tumor angiogenesis-targeting, complement activating, immune stimulating biological produced fermentatively from Group B Streptococcus. CM101 binds a capillary endothelium receptor, HP59, causing inflammatory cytokine cascades, recruiting CD69+ granulocytes to destroy neovasculature and surrounding tumor. This SBIR proposal is to determine Structure-Activity-Relationship (SAR) for CM101 to identify angiogenesis-specific HP59-targeting mechanisms and establish minimal active molecular structure (pharmacophore). CM101 is not an angiogenesis inhibitor like Avastin and related biologicals and drugs, but has a completely different mechanism of action, stimulating immune attack on HP59+ tumor neovasculature. CM101 is a promising active pharmaceutical ingredient (API) biological for cancer therapy in results from animal studies and a human Phase I safety trial published in 1997. More recent intellectual property for CM101 purification and the HP59 receptor now protects products through 2026-2028. CM101 development was interrupted by previous business failures, despite the promising technology. By establishing the pharmacophore, pinpointing biochemical binding interaction with the tumor capillary endothelium lectin receptor HP59 (See Wikipedia), we will discover mechanism of action details, new composition of matter intellectual property, and potential for development of small drug pipelines, to stimulate investors and major pharmaceutical companies' incentive to support planned Phase I/II clinical trials. In sum, CM101, the Group B Streptococcal Toxin (GBS-Toxin) is a 270Kda polysaccharide exhibits targeted binding to HP59, a specific tumor cell endothelial cell surface lectin, therefore a highly specific tumor vasculature targeting biological therapeutic, needing SAR for development. PUBLIC HEALTH RELEVANCE: This SBIR grant proposal seeks to determine the Structure-Activity-Relationship for CM101, a tumor neovasculature targeting Group B Streptococcal toxin that binds the lectin tumor angiogenesis marker HP59. HP59 binding by CM101 results in complement activation and subsequent inflammatory response against the tumor, which has been published in animal and human Phase I trials. We intend to molecularly identify the HP59 targeting mechanism, to define mechanism of action, to establish updated intellectual property, and provide potential drug pipelines by identification of a minimum pharmacophore for HP59 binding and for complement activation.