生物活性

• 描述Pyrazinamide (PZA) is an important sterilising tuberculosis drug that helps to shorten the duration of current chemotherapy regimens for tuberculosis. PZA is more active against old than against actively growing cultures. The highly diverse mutations in the PZase gene (pncA) that lead to loss of PZase activity cause PZA resistance^[2]. PZA markedly inhibited the activity of M. tuberculosis FASI (the eukaryotic-like fas1 gene), the biosynthesis of C16 to C24/C26 fatty acids from acetyl-CoA^[3]. PZA is hydrolyzed intracellularly to pyrazinoic acid (POA) by pyrazinamidase (PZase, encoded by pncA), an enzyme frequently lost in PZA-resistant strains, but the target of POA in Mycobacterium tuberculosis has remained elusive^[1]. In plant cells, PZA is converted to pyrazinecarboxylic acid (POA), suppressing the activity of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), the enzyme catalysing the final step of ethylene formation^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01994460	Pulmonary Tuberculosis Without... more >> Resistance to Rifampicin Collapse <<	Phase 2	Unknown	June 2016	Korea, Republic of ... more >> Seoul National University Bundang Hospital Recruiting Seongnam, Kyunggi, Korea, Republic of, 463-707 Contact: Jong Sun Park, MD    031-787-7054    jspark.im@gmail.com    Principal Investigator: Jong Sun Park, MD          National Medical Center Recruiting Seoul, Korea, Republic of, 100-799 Contact: Ji Yeon Lee, MD    82222607284    jedidiah125@gmail.com    Principal Investigator: Ji Yeon Lee, MD          SMG-SNU Boramae Medical Center Recruiting Seoul, Korea, Republic of, 156-707 Contact: Deog Kyeom Kim, MD    02-870-2228    kimdkmd@gmail.com    Principal Investigator: Deog Kyeom Kim, MD Collapse <<
  NCT02958709	Tuberculosis, Meningeal	Phase 1 Phase 2	Recruiting	June 2019	India ... more >> Byramji Jeejeebhoy Government Medical College and Sassoon Hospital Recruiting Pune, Maharashtra, India, 411001 Contact: Chhaya Valvi, MD       chhayavalvi@gmail.com    Contact: Vidya Mave, MD, MPH & TM    919503646148    vidyamave@gmail.com    National Institute of Research in TB and Institute of Child Health Not yet recruiting Chennai, Tamil Nadu, India, 600031 Contact: Bella Devaleenal, MBBS    919841746690    bella.d@nirt.res.in    Contact: Syed Hissar, MD, MPH    919442927242    syed.hissar@nirt.res.in    Malawi UNC Project- Malawi Not yet recruiting Lilongwe, Lilongwe District, Malawi Contact: Mina Hosseinipour, MD,MPH    2651750610    mina_hosseinipour@med.unc.edu    Contact: Tisungane Mvalo, MBBS, FCPaed    2651750610    tmvalo@unclilongwe.org Collapse <<
  NCT02153528	Tuberculosis, Pulmonary	Phase 3	Completed	-	Bangladesh ... more >> Damien Foundation Bangladesh TB project in Greater Mymensingh district (8 selected clinics) Dhaka, Greater Mymensingh district, Bangladesh Collapse <<

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• 参考文献

• [1] Shi W, Zhang X, Jiang X, et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011;333(6049):1630–1632

  [2] Zhang Y, Mitchison D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis. 2003;7(1):6–21

  [3] Zimhony O, Cox JS, Welch JT, Vilchèze C, Jacobs WR Jr. Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000;6(9):1043–1047

  [4] Sun X, Li Y, He W, et al. Pyrazinamide and derivatives block ethylene biosynthesis by inhibiting ACC oxidase. Nat Commun. 2017;8:15758. Published 2017 Jun 12