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本帖最后由 hbv_challenger 于 2015-12-29 21:19 编辑
看看CPI-431-32是如何夸自己的药的,如果疗效确定,大伙就受益了.http://www.ciclofilin.com/cpi-431-32.html
CPI-431-32 has the potential to be a backbone treatment for chronic hepatitis B.
CPI-431-32有望成为HBV治疗的生力军.
CPI-431-32 is a potent cyclophilin inhibitor designed and synthesized by Ciclofilin Pharmaceuticals and our lead drug candidate for chronic hepatitis B. CPI-431-32 was identified through an extensive process of in-house screening, optimization, and third-party validation. CPI-431-32 is a lead candidate primarily due to potent antiviral activity towards hepatitis B virus (HBV), the causative agent of chronic hepatitis B. However, CPI-431-32 also demonstrates anti-fibrotic properties which occur independently of its effects on HBV. Thus, we propose that CPI-431-32 would benefit hepatitis B patients not only by lowering and possibly eliminating HBV but also by directly reducing fibrosis, a major contributor to cirrhosis and development of liver cancer.
CPI-431-32 has the potential to alleviate HBV-induced liver disease well beyond that seen with current treatments.
CPI-431-32是由Ciclofilin Pharmaceuticals 公司设计和合成的一个强有力的亲环蛋白抑制剂.它有一个全面深入筛选,优化和第三方验证的过程.它是HBV的潜在的首选治疗药物.而且,它在抗纤维化方面也表现了独立的效果.所以,我们认为它对HBV患者,不单单是可能降低和消除HBV,而且直接抗纤维化,纤维化是硬化和癌化的一个主要因素.它有望在比现在其它治疗药物更优秀.
How does CPI-431-32 inhibit the hepatitis B virus?
CPI-431-32 inhibits HBV by virtue of its ability to block the interaction of HBV proteins with host cell cyclophilins which the virus uses to propagate infection and avoid detection by the cell's antiviral mechanisms. The "hijacking" of host cell cyclophilins is not unique to HBV; other viruses do the same, including hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1). Experiments have shown that CPI-431-32 blocks multiple activities of HBV within cells: DNA replication, HBeAg and HBsAg production, and generation of cccDNA. There is evidence that CPI-431-32 may accomplish this in part by stimulating interferon responses, the cell's most important, natural antiviral defense mechanism. Finally, CPI-431-32 also blocks the entry of HBV into cells via the NTCP receptor in a cyclophilin-independent manner, which may reduce chronic infection through yet another mechanism.
CPI-431-32如何抑制HBV?
CPI-431-32通过阻断HBV蛋白和宿主亲环蛋白之间的交互来发挥作用. 正是由于这种交互,病毒可以产生感染和逃避细胞的反病毒机制.
这种"绑架"宿主的亲环蛋白不单单是HBV这样做,其它很多病毒都是这样子的,如HCB,HIV-1等等.
实验证明,CPI-431-32能够阻断HBV蛋白和宿主亲环蛋白的多条通道,DNA的复制,HbeAg,HBsAG的生成,以及cccDNA的产生.
有证据表明,CPI-431-32能够达到这些功能,可能是激起了类似干扰素的反应,也就是细胞本身的自然抗病毒的保护机制.最后,CPI-431-32也可以以亲环蛋白独立的方式阻断HBV通过NTCP接收器进入细胞内,这样就减少了对另外一个机体的感染.
What is the evidence that CPI-431-32 is anti-fibrotic?
Many studies have demonstrated that cyclophilin inhibition reduces injury to the liver and other organs arising from excessive inflammation and fibrosis. Fibrosis is the scarring response to injury which deteriorates organ function and is a major cause of cirrhosis in hepatitis B. Ciclofilin Pharmaceuticals contracted Stelic Institute Inc. (Tokyo, Japan) to conduct a study with CPI-431-32 in the STAM mouse model in which animals develop liver inflammation, fibrosis, and hepatocellular carcinoma in similarity to the progression of liver disease in chronic hepatitis B. CPI-431-32 reduced the extent of fibrosis by 55% with 3 weeks of treatment. These results suggest that CPI-431-32 directly targets the molecular events that cause fibrosis and therefore could limit or reverse liver damage associated with chronic infection in patients.
有什么证据说明 CPI-431-32有抗纤维化的功能?
很多个研究表明亲环蛋白抑制可以减少肝和其它器管在发炎和纤维化的情形下受到的伤害.
纤维化就是器管受伤后结痂.结痂后器管功能会恶化,进而硬化.
日本的Ciclofilin Pharmaceuticals公司进行了一项对比研究,在STAM老鼠的肝炎,纤维化,肝癌的发现过程当中,用CPI-431-32治疗3周,纤维化减少55%.这个结果说明,CPI-431-32直接作用到引起纤维化的分子事件,限制和逆反了跟HBV当中的肝损.
Is CPI-431-32 safe to be administered to patients?
Studies need to be conducted to establish the safety of CPI-431-32 in humans, but to date the drug has not demonstrated any overt signs nor biochemical markers of toxicity in animal studies. The safety of CPI-431-32 is also backed up by the fact that a structurally-related drug, cyclosporin A, has been used safely in patients for over 30 years.
CPI-431-32安全吗?
一定要进行相关的研究来取得CPI-431-32在人类当中的使用安全.到目前为止,在动物试验当中还没有表现出明显的毒性.
它的安全性也有结构性类似的药物(cyclosporin A)来撑腰.大伙都知道,cyclosporin A已经安全使用30多年了.
Would CPI-431-32 provian advantage over other drugs?
Yes, CPI-431-32 could provide many advantages over existing drugs:
CPI-431-32 affects multiple stages of the HBV life cycle, providing higher likelihood of HBV eradication and fewer medications; existing nucleos(t)ide analogs target only HBV polymerase activity
CPI-431-32 reduces HBV through virus-targeting and immunodulatory mechanisms; existing medications act through one or the other mechanisms but not both simultaneously
CPI-431-32 could reduce liver injury through two distinct mechanisms - antiviral and anti-fibrotic; current drugs are only antiviral
CPI-431-32 can be administered orally; interferon-α and multiple drug candidates in development (e.g. RNAi) must be injected
CPI-431-32 has a high threshold to development of drug resistance; some existing drugs have a low threshold, meaning that they frequently become ineffective in patients over time due to
mutations in the virus
CPI-431-32优于其它药物吗?
这个自然. 相比现有的药物,CPI-431-32 优势如下:
CPI-431-32 影响HBV生命周期的多个通道,提供更高的扑杀HBV的可能性.相比而言,NUC只作用于HBV聚合酶;
CPI-431-32 通过作用攻击病毒和提高免疫来减少病毒数量,现有的疗法只能起一种作用.不能同时起两种作用;
CPI-431-32 可以通过抗病毒和抗纤维化两种方式来减少肝损.其它药物只能抗病毒;
CPI-431-32 可口服,干扰素和多个候选药物必须注射;
CPI-431-32 高门槛耐药,一些现有药物的耐药门槛低得可怜,长时间吃药,病毒变异,治疗变得无效.
Where is CPI-431-32 in its development?
Preclinical studies are underway towards the filing of an Investigation New Drug (IND) application.
CPI-431-32到了哪个阶段了?
正在进行新药申请的临床前研究.
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发表于 2015-12-29 15:00
