Current Status and Research Strategies in Tuberculosis Drug Development

被引:110
作者
Dover, Lynn G. [2 ]
Coxon, Geoffrey D. [1 ]
机构
[1] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland
[2] Northumbria Univ, Biomol & Biomed Res Ctr, Sch Life Sci, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England
基金
英国医学研究理事会;
关键词
EARLY BACTERICIDAL ACTIVITY; MYCOBACTERIUM-TUBERCULOSIS; ANTITUBERCULOSIS DRUGS; RESISTANT TUBERCULOSIS; IN-VITRO; MOXIFLOXACIN; ETHIONAMIDE; ETHR; EPIDEMIOLOGY; ACTIVATION;
D O I
10.1021/jm200305q
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
There is no doubt that the future success in the battle to end the scourge of this debilitating disease relies heavily on the discovery of new drugs. At the moment there are a worryingly low number of potential new chemical entities in the TB drug pipeline. To overcome the high rates of attrition, many more need to be discovered and developed. To ensure this, a growing and sustainable supply of new drug discovery and development programmes must be fostered by highly multidisciplinary collaborative partnerships. This will only be possible by the growing number of academic, pharmaceutical, and not for profit organization collaborations having access to open and available data, compound libraries, and expertise to assist all involved in such research initiatives. Support for clinical trials to evaluate a steady supply of promising compounds is critical as well as funding to sustain biomarker research to provide surrogate end points to accelerate candidate selection during drug discovery and dose selection in early clinical research and ultimately to shorten the time to licensing of new drugs. As combination therapy is unavoidable and treatment of HIV co-infection is of paramount importance, funding must also be made available to address the inherent pharmacokinetic issues raised. Critical to the success of these strategies is sustained financial and legislative support from the public sector to ensure that TB drug discovery remains a viable and attractive proposition for academia and pharmaceutical companies to engage with as they did in the mid-20th century. This paradigm shift in the way that TB drug discovery research is coordinated and conducted is vital for its success, and the time for its implementation is now! © 2011 American Chemical Society.
引用
收藏
页码:6157 / 6165
页数:9
相关论文
共 67 条
  • [31] Genetic analysis of the β-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to β-lactam antibiotics
    Flores, AR
    Parsons, LM
    Pavelka, MS
    [J]. MICROBIOLOGY-SGM, 2005, 151 : 521 - 532
  • [32] Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis
    Frénois, F
    Engohang-Ndong, J
    Locht, C
    Baulard, AR
    Villeret, V
    [J]. MOLECULAR CELL, 2004, 16 (02) : 301 - 307
  • [33] Discovery and validation of new antitubercular compounds as potential drug leads and probes
    Goldman, Robert C.
    Laughon, Barbara E.
    [J]. TUBERCULOSIS, 2009, 89 (05) : 331 - 333
  • [34] Natural products, small molecules, and genetics in tuberculosis drug development
    Gutierrez-Lugo, Maria-Teresa
    Bewley, Carole A.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (09) : 2606 - 2612
  • [35] PYRAZINAMIDE STERILIZING ACTIVITY INVITRO AGAINST SEMIDORMANT MYCOBACTERIUM-TUBERCULOSIS BACTERIAL-POPULATIONS
    HEIFETS, L
    LINDHOLMLEVY, P
    [J]. AMERICAN REVIEW OF RESPIRATORY DISEASE, 1992, 145 (05): : 1223 - 1225
  • [36] HOBBY GL, 1957, AM REV TUBERC PULM, V76, P1031
  • [37] Meropenem-Clavulanate Is Effective Against Extensively Drug-Resistant Mycobacterium tuberculosis
    Hugonnet, Jean-Emmanuel
    Tremblay, Lee W.
    Boshoff, Helena I.
    Barry, Clifton E., III
    Blanchard, John S.
    [J]. SCIENCE, 2009, 323 (5918) : 1215 - 1218
  • [38] Antituberculosis drugs: Ten years of research
    Janin, Yves L.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (07) : 2479 - 2513
  • [39] Pharmacodynamics and pharmacokinetics of SQ109, a new diamine-based antitubercular drug
    Jia, J
    Tomaszewski, JE
    Hanrahan, C
    Coward, L
    Noker, P
    Gorman, G
    Nikonenko, B
    Protopopova, M
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2005, 144 (01) : 80 - 87
  • [40] Johnson JL, 2006, INT J TUBERC LUNG D, V10, P605