导读： ICA-17043 29 现名为senicapoc(一种新型的Gardos离子通道抑制剂，用于镰状细胞贫血症）。IDN-6556是Idun领先开发的广谱级联反应酶caspase抑制剂，IDN-6556可用于治疗饮酒过度引起的肝病及丙肝（HCV）。伊罗夫文(IROFULVEN)治疗晚期胰腺癌。哌立福新(PERIFOSINE，KRX-0401) 31 口服活性烷基磷酯化合物，具有抗肿瘤活性。

23. ICA-17043 29 现名为senicapoc(一种新型的Gardos离子通道抑制剂，用于镰状细胞贫血症）ICA-17043 is a novel small molecule ion channelion channel  inhibitor under development for the chronic prophylactic treatment of sickle cell disease.  This novel drug candidate is taken orally and is being developed for once-a-day dosing. ICA-17043 has received both fast track designation and orphan drug designation from the U.S. Food and Drug Administration. ICA-17043 targets a particular potassium channel, called the Gardos channel, that is located on the membrane of red blood cells. In collaboration with the McNeil Pediatrics Division of McNeil-PPC, Inc., Icagen is currently conducting a Phase III clinical trial of ICA-17043. About Sickle Cell Disease Sickle cell disease is a chronic and debilitating genetic blood disorder, primarily affecting individuals of African descent, resulting in a variety of disease complications and a significantly shortened lifespan in the majority of patients. Sickle cell disease is the most common genetic disease among individuals of African descent and is prevalent worldwide. According to the American Medical Association, there are approximately 100,000 patients with sickle cell disease in the United States.

24. IDN-6556 29
IDN-6556是Idun领先开发的广谱级联反应酶caspase抑制剂，IDN-6556可用于治疗饮酒过度引起的肝病及丙肝（HCV），IDN-6556是首个广谱级联反应酶抑制剂，可特异性作用于人体细胞凋亡中的级联反应酶。（Idun制药公司已被辉瑞公司收购）

25. 伊罗夫文(IROFULVEN) 29
在阿姆斯特丹召开的第11届NCI-EORTC-AACR抗癌新药研讨会上，研究人员报道了这项II期临床实验结果。该结果显示，在参与irofulven实验的53名患者中，有10例生存达到了6个月，即该研究的观察终点。同样重要的是，有2位患者的病情在客观上出现了好转。其中一个患者经治疗后肿瘤发生了消退，另一个患者的肿瘤体积缩小了84%。
基于以上结果，研究人员计划在年底开始再次收集病人，以进行irofulven治疗耐受gemcitabine化疗的晚期胰腺癌的III期临床试验。而该实验的最终计划和步骤，还要与美国食品药物管理局(FDA)进一步讨论后决定。
亚利桑那州癌症研究中心主席，医学教授Daniel Von Hoff博士说，这II期试验提示irofulven对那些晚期的难治性胰腺癌患者有效。这些发现与I期临床试验和临床前期研究的结果相符合。为在对gemcitabine治疗无效的晚期胰腺癌患者中进行III期临床试验提供了基础。并且，最近的一项剂量优化试验结果表明，irofulven的耐受性已经得到了很大改善。加上与FDA的讨论结果令人鼓舞，因而，进一步开展III期临床实验就很容易被理解。他相信收集患者的工作不久就可开始。
II期试验的治疗阶段已顺利完成，最终数据的分析正在进行中。试验中，对gemcitabine治疗无效而又无法手术的晚期胰腺癌患者进行Irofulven治疗，连续5天每天5分钟静脉注射，28天后再次重复给药。该药最常见的副作用包括恶心，呕吐，疲劳和骨髓抑制。
在即将进行的III期临床试验中，患者将被随机分成两组，分别给予irofulven或5-氟尿嘧啶，后者是目前常用的晚期胰腺癌的化疗药物。接受irofulven的患者将使用新的疗程安排。方法是，每隔一周接受一次irofulven治疗。近期进行的一个剂量优化试验证实，这种新的疗程安排在不影响疗效的同时可极大地改善患者对同等剂量药物的耐受性。III期临床实验将采用中位生存期作为研究的初级观察终点，肿瘤的客观反应和临床症状的改善等指标作为次级观察终点。最终，这项III期临床实验的结果将成为公司向FDA申请新药的文件的一部分。
据美国癌症学会估计，今年全美有28,300例新发胰腺癌患者，其中有28,200例面临死亡。早期胰腺癌患者常没有症状，而患者一旦被发现为胰腺癌，通常已经处于晚期。并且，化疗对胰腺癌收效甚微。胰腺癌的5年生存率只有4%。由于胰腺癌的预后太差，所以即使是临床症状的适度改善，也被认为是治疗上的重大进展。
第11届NCI-EORTC-AACR研讨会上的另一个研究资料进一步阐明了irofulven的作用机制。 新的研究结果证明：(a)即使很高浓度的抗凋亡蛋白Bcl-2也不能完全阻断irofulven引起肿瘤细胞凋亡；(b)irofulven的前凋亡效应可能是通过与DNA共价结合、激活死亡信号途径，或与细胞蛋白结合、破坏氧化还原平衡而实现的；(c)irofulven可以以浓度依赖的方式抑制端粒酶阳性的细胞系生长，并能抑制端粒酶的活性。

26. 哌立福新(PERIFOSINE，KRX-0401) 31 口服活性烷基磷酯化合物，具有抗肿瘤活性。 perifosine（Akt inhibitor）is an alkylphospholipid exhibiting antitumor properties and is currently in phase II clinical trials for various types of cancer. The mechanisms by which perifosine exerts its antitumor effects, including the induction of apoptosis, are not well understood. The current study focused on the effects of perifosine on the induction of apoptosis and its underlying mechanisms in human non–small cell lung cancer (NSCLC) cells. Perifosine, at clinically achievable concentration ranges of 10 to 15 μmol/L, effectively inhibited the growth and induced apoptosis of NSCLC cells. PerifosineinhibitedAktphosphorylation and reduced the levels of total Akt. Importantly, enforced activation of Akt attenuated perifosine-induced apoptosis. These results indicate that Akt inhibition is necessary for perifosine-induced apoptosis. Despite the activation of both caspase-8 and caspase-9, perifosine strikingly induced the expression of the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor, death receptor 5, and down-regulated cellular FLICE-inhibitory protein (c-FLIP), an endogenous inhibitor of the extrinsic apoptotic pathway, with limited modulatory effects on the expression of other genes including Bcl-2, Bcl-XL, PUMA, and survivin. Silencing of either caspase-8 or death receptor 5 attenuated perifosine-induced apoptosis. Consistently, further down-regulation of c-FLIP expression with c-FLIP small interfering RNA sensitized cells to perifosine-induced apoptosis, whereas enforced overexpression of ectopic c-FLIP conferred resistance to perifosine. Collectively, these data indicate that activation of the extrinsic apoptotic pathway plays a critical role in perifosine-induced apoptosis. Moreover, perifosine cooperates with TRAIL to enhance the induction of apoptosis in human NSCLC cells, thus warranting future in vivo and clinical evaluation of perifosine in combination with TRAIL in the treatment of NSCLC. An orally active alkyl-phosphocholine compound with potential antineoplastic activity. Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. Perifosine has a lower gastrointestinal toxicity profile than the related agent miltefosine.