新的TB用藥概念，可殺latent TB，讓TB的protein沒法degredattion!!
非常了不起
大部份抗生素都是趁細菌在replication的時候下手殺菌
但對TB這種難得分裂的細菌就無法下手
所以才要高劑量長時間的給予，讓病人受苦
但冬眠的細菌仍要大便
把大便筒塞住他就完了
所以這個藥如果ok
可以大幅度縮短TB療程
New Approach to Treating Tuberculosis
Targeting nonreplicative bacteria might avert long courses of therapy for TB patients.
In contrast to most bacterial pathogens, Mycobacterium tuberculosis is a slow-growing organism with a propensity for latency, which means that patients with this infection require treatment with multiple drugs for many months. To remain healthy, every cell, including single-cell organisms, requires proper levels of each protein that it produces. This fact means that a balance must exist between synthesis and degradation of proteins. Many antibacterials target synthesis of bacterial proteins, but none inhibit degradation of proteins. Unlike other bacteria, mycobacteria have proteasomes — a key site of protein degradation — and might be susceptible to inhibitory agents.
A multi-institutional team has identified a class of compounds that inhibit proteasomes in M. tuberculosis without inhibiting proteasomes in human cells. The team reports that two compounds, GL5 and HT1171, rapidly, powerfully, and permanently inhibit mycobacterial proteasomes and kill mycobacteria that are in a latent nonreplicating state. At concentrations necessary to kill bacteria, the compounds demonstrated no toxicity to animal (eukaryotic) cells.
Comment: Antibacterials that target synthesis of M. tuberculosis proteins have been only moderately successful for treating infection. The long multidrug courses of therapy that are required to treat tuberculosis often lead to patient nonadherence and to development of drug-resistant organisms. This new approach to targeting degradation of M. tuberculosis proteins appears — at this very early stage — to be both a potent and nontoxic approach to treating one of the world's great killers. As such, this development is very exciting.
— Anthony L. Komaroff, MD
Published in Journal Watch General Medicine October 13, 2009
Citation(s):
Lin G et al. Inhibitors selective for mycobacterial versus human proteasomes. Nature 2009 Oct 1; 461:621. (http://dx.doi.org/10.1038/nature08357)
* Medline abstract (Free)
https://docs.google.com/fileview?id=0B278nGJMQBk7M2UzNjgxZWEtMmU3ZS00MTAxLTljYzAtNjMwMDQzNjRlMjZh&hl=zh_TW
http://docs.google.com/present/edit?id=0AW78nGJMQBk7ZGc1d3FjYmpfMjMwaGdkNHJmZG4&hl=zh_TW
大部份抗生素都是趁細菌在replication的時候下手殺菌
但對TB這種難得分裂的細菌就無法下手
所以才要高劑量長時間的給予，讓病人受苦
但冬眠的細菌仍要大便
把大便筒塞住他就完了
所以這個藥如果ok
可以大幅度縮短TB療程
New Approach to Treating Tuberculosis
Targeting nonreplicative bacteria might avert long courses of therapy for TB patients.
In contrast to most bacterial pathogens, Mycobacterium tuberculosis is a slow-growing organism with a propensity for latency, which means that patients with this infection require treatment with multiple drugs for many months. To remain healthy, every cell, including single-cell organisms, requires proper levels of each protein that it produces. This fact means that a balance must exist between synthesis and degradation of proteins. Many antibacterials target synthesis of bacterial proteins, but none inhibit degradation of proteins. Unlike other bacteria, mycobacteria have proteasomes — a key site of protein degradation — and might be susceptible to inhibitory agents.
A multi-institutional team has identified a class of compounds that inhibit proteasomes in M. tuberculosis without inhibiting proteasomes in human cells. The team reports that two compounds, GL5 and HT1171, rapidly, powerfully, and permanently inhibit mycobacterial proteasomes and kill mycobacteria that are in a latent nonreplicating state. At concentrations necessary to kill bacteria, the compounds demonstrated no toxicity to animal (eukaryotic) cells.
Comment: Antibacterials that target synthesis of M. tuberculosis proteins have been only moderately successful for treating infection. The long multidrug courses of therapy that are required to treat tuberculosis often lead to patient nonadherence and to development of drug-resistant organisms. This new approach to targeting degradation of M. tuberculosis proteins appears — at this very early stage — to be both a potent and nontoxic approach to treating one of the world's great killers. As such, this development is very exciting.
— Anthony L. Komaroff, MD
Published in Journal Watch General Medicine October 13, 2009
Citation(s):
Lin G et al. Inhibitors selective for mycobacterial versus human proteasomes. Nature 2009 Oct 1; 461:621. (http://dx.doi.org/10.1038/nature08357)
* Medline abstract (Free)
https://docs.google.com/fileview?id=0B278nGJMQBk7M2UzNjgxZWEtMmU3ZS00MTAxLTljYzAtNjMwMDQzNjRlMjZh&hl=zh_TW
http://docs.google.com/present/edit?id=0AW78nGJMQBk7ZGc1d3FjYmpfMjMwaGdkNHJmZG4&hl=zh_TW
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