IGF::OT::IGF: SBIR Phase II, Topic 326: Development of Novel Therapeutic Agents that Target Cancer

在过去的十年里，人们已经非常清楚，消除致癌干细胞（CSC）是“治愈”癌症的必要条件。不幸的是，大多数现有的临床治疗方法针对的是大肿瘤，而忽略了极少数的CSCs（占肿瘤的<~1%），这些CSCs在治疗完成后扩大并导致复发。Transgenex Nanobiotech Inc. （TGN）的研发已经证明了靶向利钠肽受体A （NPRA）阻止肿瘤进展的可行性，然而NPRA在CSCs中的作用尚不清楚。在第一阶段合同中，TGN的科学家们通过计算机建模开发了一个小分子库，并筛选了它们针对CSC的能力。这导致了化合物#2（迄今为止指定为NRI20152）作为真正的NPRA抑制剂的鉴定和验证。NRI20152在3代球化实验中显示出抗csc活性，在中试急性毒性研究中对小鼠无有害作用。

Over the past decade, it has become abundantly clear that cancer-initiating stem cell (CSC) elimination is imperative to ‘cure’ cancer. Unfortunately, most of the existing clinical therapies target the bulk tumor and spare the very small number CSCs comprising <~1% of tumor, which expand after completion of therapy and cause relapse. Transgenex Nanobiotech Inc. (TGN) R & D has demonstrated the feasibility of targeting natriuretic peptide receptor A (NPRA) to cease tumor progression, however NPRA’s role in CSCs was unclear. In the phase I contract, TGN scientists developed a library of small molecules by computer modelling and screened them for their capacity to target CSC. This led to identification and validation of compound #2, heretofore designated NRI20152, as a bona-fide inhibitor of NPRA. NRI20152 showed anti-CSC activity in 3 generations of sphere-forming assays and it showed no harmful effect in mice in the pilot acute toxicity studies.