Preclinical Pharmacology of the anti-Ras drug, FTS

描述（由申请人提供）：癌基因编码诱导细胞增殖的蛋白质。 经历恶性转化致癌Ras是存在于细胞中的这样一种蛋白质， 90%的胰腺癌和1/3的人类癌症。蒂雷奥斯 该公司已获得许可的药物， 细胞膜中的锚定位点。这些药物抑制Ras依赖的人 在裸鼠中生长的肿瘤。在引起肿瘤的剂量下没有毒性作用 回归分析向FDA注册Ras拮抗剂用于癌症治疗是一个挑战。 Thyreos的主要目标。这笔赠款的具体目标是完成 该过程的下一步：我们将继续进行临床前药理学研究， Ras拮抗剂FTS在移植人肿瘤的裸鼠中的应用。的 研究将证明FTS对人类肿瘤的剂量反应效应， 与标准化疗的协同作用，给药频率， 最大耐受剂量、负荷剂量的需要和药物的持续时间 自由时间。的药代动力学、代谢、分布和排泄 将研究小鼠和大鼠的FTS。虽然Thyreos完成这些研究， 在具体目标中概述，它将完成临床前的剩余部分 发展因此，在第二阶段补助金结束时，Thyreos将能够提交 1/2期研究的IND。FTS作用于新发现的癌症靶点。到 据我们所知，没有其他药物正在开发， 作为FTS的作用机制。

DESCRIPTION (provided by applicant): Oncogenes encode proteins that induce cell to undergo malignant transformation. Oncogenic Ras is such a protein present in 90 percent of pancreatic carcinomas and 1/3 of all human cancers. Thyreos Corporation has licensed drugs that inactivate Ras by displacement from its anchorage site in the cell membrane. These drugs inhibit Ras-dependent human tumors grown in nude mice. There are no toxic effects at doses that cause tumor regression. To register Ras antagonists with the FDA for cancer therapy is a major goal of Thyreos. The specific aims of this grant will be to complete the next steps in this process: we will continue the preclinical pharmacology on the Ras-antagonist, FTS, in nude mice with transplants of human tumors. The studies will demonstrate the dose response effects of FTS on human tumors, its synergism with standard chemotherapy, the frequency of drug administration, the maximal tolerated doses, the need for a loading dose and the duration of a drug free period. The pharmacokinetics, metabolism, distribution and excretion of FTS in mice and rats will be studied. While Thyreos completes these studies as outlined in the Specific Aims it will complete the remainder of preclinical development. Thus at the end of the Phase II grant Thyreos will be able to file an IND for a phase 1/2 study. FTS acts on a newly identified cancer target. To our knowledge there is no other drug being developed that has the same mechanism of action as FTS.