Ranpirnase:两栖类核糖核酸酶A,第30页protein-alfacell。

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Ranpirnase:两栖类核糖核酸酶A,第30页protein-alfacell。

药物R d . 2007; 8 (2): 120 - 4。

PubMed ID

17324010 (在PubMed

]

文摘

Ranpirnase [Onconase]是一种两栖动物的卵母细胞和早期胚胎核糖核酸酶(核糖核酸酶)的105个氨基酸长度能够控制肿瘤生长的肿瘤细胞内降解RNA,导致抑制蛋白质合成和逮捕在G(1)有丝分裂阶段。它代表了第一个成功的隔离,净化和描述oocytic /早期胚胎因子能够控制细胞生长的早期胚胎组织的活动。Alfacell公司目前正在进行临床试验的患者ranpirnase不可切除的恶性间皮瘤和非小细胞肺癌。该公司可能启动二期临床试验在2006年乳腺癌和食道癌。Alfacell扩大与美国国家癌症研究所研究协议在2002年9月,允许NCI检查ranpirnase作为辐射增强剂的影响。然而,调查在此用ranpirnase现在似乎停止了。Alfacell正在确认阶段希望注册试验ranpirnase +阿霉素与阿霉素在不可切除的恶性间皮瘤患者超过360人,并将评估生存作为主要的端点。有针对性的治疗组在这个实验中代表90%的恶性间皮瘤患者在诊断时。试验正在进行的美国、加拿大、波兰、意大利、德国、澳大利亚、新西兰、俄罗斯、罗马尼亚、墨西哥和巴西。2006年4月,共有210个事件(病人死亡),代表三分之二的所需的研究活动。 Results from the protocol-specified first interim analysis based on one-third of the required events have been reported and the company has the option to conduct a second interim analysis of the data at any point after 210 events. A final analysis will be undertaken at 316 events. Alfacell completed a phase III trial of single-agent ranpirnase in patients with unresectable malignant mesothelioma in April 1999. The efficacy of ranpirnase was compared with that of doxorubicin (head-to-head). The primary objectives were overall survival, progression-free survival and quality of life. In preclinical studies, ranpirnase demonstrated significant activity against neuroblastoma, rhabdomyosarcoma and chemotherapy-resistant variants of these cancer cells. Development for these indications has been discontinued. Preclinical investigations conducted by Alfacell showed synergistic antitumour effects between ranpirnase and proteasome inhibitors. However, development is this area has been discontinued. Alfacell announced in May 2003 that it would be providing ranpirnase to the federal severe acute respiratory syndrome (SARS) testing programme for evaluation against the human coronavirus implicated in the disease. No further development has been reported. Alfacell has received nine US and four European patents for ranpirnase. Patents issued in the US range from the 1996-issued patent (No. 5 559 212) covering the amino acid sequence of ranpirnase, to the patent (No. 6 175 003 B1) issued in January 2001 protecting the gene sequences of the compound plus another genetically engineered variant, effectively protecting the company's proprietary technology. In August 2002, Alfacell received a US patent (No. 6 423 515 B1) entitled 'Methods of Making Nucleic Acids Encoding Ribonucleases'. This patent is effective until 2020.

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药物

Ranpirnase

药物靶点

药物	目标	类	生物	药理作用	行动
Ranpirnase	DNA	核苷酸	人类	未知的	不可用	细节