A PHASE 1 SAFETY AND PHARMACOKINETIC STUDY OF SU011248 AND CAPECITABINE IN PA

SU011248 和卡培他滨在 PA 中的 1 期安全性和药代动力学研究

• 批准号: 7379149
• 负责人: CHRISTOPHER J SWEENEY
• 金额: $ 0.02万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379149
• 关键词: PHASE; SAFETY; PHARMACOKINETIC; STUDY; SU011248

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Receptor tyrosine kinases (RTKs) are transmembrane proteins containing extracellular ligand-binding domains and intracellular catalytic domains. RTKs are activated following binding of their cognate ligands and many of the processes involved in tumor growth, progression and metastases are mediated by signaling molecules acting downstream from these proteins [1, 2]. Several members of the split-kinase domain family of RTKs are implicated in deregulated/autocrine proliferation and survival of solid and hematologic cancer cells. These include the platelet-derived growth factor receptors (PDGFR and ); vascular endothelial growth factor receptors (VEGFR) Type 1 and 2 (FLT1 and FLK 1/KDR); the stem cell factor (SCF) receptor, KIT; and the FLT3-ligand receptor. In addition RTKs PDGFR and VEGFR are implicated in tumor-dependent angiogenesis. SU011248 is a small molecule with the molecular formula C22H27FN4O2. The free base has a molecular weight of 398.48 and the L-malate salt, the form used in clinical trials (Error! Reference source not found.), has a molecular weight of 532.57. The chemical name of the L-malate salt is 5-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethylpyrrole-3-carbo ylic acid (2-diethylamino-ethyl)-amide, compound with (S)-2-hydroxy-succinic acid 1:1.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。受体酪氨酸激酶（RTK）是含有细胞外配体结合结构域和细胞内催化结构域的跨膜蛋白。RTK在其同源配体结合后被激活，并且参与肿瘤生长、进展和转移的许多过程由在这些蛋白质下游起作用的信号分子介导[1，2]。RTK的分裂激酶结构域家族的几个成员涉及实体和血液癌细胞的失调/自分泌增殖和存活。这些包括血小板衍生生长因子受体（PDGFR和）;血管内皮生长因子受体（VEGFR）1型和2型（FLT 1和FLK 1/KDR）;干细胞因子（SCF）受体，KIT;和FLT 3-配体受体。此外，RTKs、PDGFR和VEGFR与肿瘤依赖性血管生成有关。 SU 011248是一种小分子，分子式为C22 H27 FN 4 O2。游离碱的分子量为398.48，L-苹果酸盐是临床试验中使用的形式（错误！未找到参考源），分子量为532.57。L-苹果酸盐的化学名称为5-（5-氟-2-氧代-1，2-二氢-吲哚-3-亚基甲基）-2，4-二甲基吡咯-3-甲酸（2-二乙氨基-乙基）-酰胺，与（S）-2-羟基-琥珀酸的化合物为1：1。