TMC207: the first compound of a new class of potent anti-tuberculosis drugs.
TMC207: the first compound of a new class of potent anti-tuberculosis drugs.
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DOI：
10.2217/fmb.10.50
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发表时间：
2010-06
影响因子：
3.1
通讯作者：
Kritski A
中科院分区：
文献类型：
--
作者：
Matteelli A;Carvalho AC;Dooley KE;Kritski A
结核分枝杆菌引起的疾病继续成为全球流行病：超过 20 亿人存在潜伏性结核感染，新增结核病例超过 900 万，其中 50 万具有多重耐药性 (MDR)，估计每年有近 200 万人死亡。需要新药来缩短药物敏感结核病的治疗时间和治疗耐多药结核病。 TMC207 是一种一流的二芳基喹啉化合物，具有新颖的作用机制，可抑制细菌 ATP 合酶，并对药物敏感和耐药结核病具有有效活性。它对结核分枝杆菌和其他分枝杆菌具有杀菌和消毒活性，但对其他细菌几乎没有活性。在一项对服用 TMC207 加标准背景方案的耐多药结核病患者进行的 II 期疗效研究中，该药物似乎安全且耐受性良好，并且在治疗 2 个月后显示出显着疗效，痰培养转化率为 48%（安慰剂组为 9%）。鉴于 Tibotec 和结核病联盟之间的产品开发合作伙伴关系，在较短的一线治疗方案中使用 TMC207 或在耐药结核分枝杆菌感染的二线治疗方案中使用 TMC207 的策略都在推行中。尚未发表TMC207在合并HIV感染的结核病患者中的临床数据；抗逆转录病毒药物之间的药物相互作用研究正在进行中。最后，TMC207卓越的杀菌能力也使其成为消除结核病策略中颇具吸引力的药物。当前和未来的研究将确定TMC207在药物敏感结核病的缩短治疗方案、耐多药结核病的更有效和耐受性更好的方案、潜伏性结核感染的治疗以及间歇性结核病治疗方案中的作用。
Disease caused by Mycobacterium tuberculosis continues as a global epidemic: over 2 billion people harbor latent TB infection, and more than 9 million new TB cases, of whom 500,000 are multidrug-resistant (MDR), and nearly 2 million deaths are estimated to occur each year. New drugs are required to shorten treatment duration of drug-sensitive TB and for the treatment of MDR-TB. TMC207 is a first-in-class diarylquinoline compound with a novel mechanism of action, the inhibition of bacterial ATP synthase, and potent activity against drug-sensitive and drug-resistant TB. It has bactericidal and sterilizing activity against M. tuberculosis and other mycobacterial species, but little activity against other bacteria. In a Phase II efficacy study conducted in patients with MDR-TB taking TMC207 plus a standard background regimen, the drug appeared to be safe and well tolerated, and showed significant efficacy after 2 months of treatment with conversion rates of sputum culture of 48% (vs 9% in the placebo group). Given the product development partnership between Tibotec and the TB Alliance, the strategies of using TMC207 in shorter first-line regimens or using it in second-line regimens for drug-resistant M. tuberculosis infections are both being pursued. No clinical data of TMC207 in TB patients with HIV coinfection have been published; drug–drug interaction studies with antiretrovirals are being conducted. Finally, the remarkable sterilizing capacity of TMC207 also makes it an attractive drug in the strategy of TB elimination. Current and future studies will determine the role of TMC207 in a shortened treatment regimen for drug-sensitive TB, a more effective and better-tolerated regimen for MDR-TB, the treatment of latent TB infection, and intermittent-TB treatment regimens.