A clinical drug library screen identifies astemizole as an antimalarial agent

被引：220
作者：
Chong, Curtis R.
Chen, Xiaochun
Shi, Lirong
O Liu, Jun
Sullivan, David J., Jr. [1 ]
机构：
[1] Johns Hopkins Univ, Sch Med, Johns Hopkins Clin Compound Screening Initiat, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Med Sci Training Program, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
来源：
NATURE CHEMICAL BIOLOGY | 2006年 / 2卷 / 08期
关键词：
D O I：
10.1038/nchembio806
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The high cost and protracted time line of new drug discovery are major roadblocks to creating therapies for neglected diseases. To accelerate drug discovery we created a library of 2,687 existing drugs and screened for inhibitors of the human malaria parasite Plasmodium falciparum. The antihistamine astemizole and its principal human metabolite are promising new inhibitors of chloroquine-sensitive and multidrug-resistant parasites, and they show efficacy in two mouse models of malaria.
引用
收藏
页码：415 / 416
页数：2
相关论文
共 10 条
  • [1] Toward a pharmacophore for drugs inducing the long QT syndrome:: Insights from a CoMFA study of HERG K+ channel blockers
    Cavalli, A
    Poluzzi, E
    De Ponti, F
    Recanatini, M
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (18) : 3844 - 3853
  • [2] Antihistamine drug withdrawn by manufacturer
    Gottlieb, S
    [J]. BRITISH MEDICAL JOURNAL, 1999, 319 (7201) : 7 - 7
  • [3] CHEMICAL DEVELOPMENT OF ASTEMIZOLE-LIKE COMPOUNDS
    JANSSENS, F
    JANSSEN, MAC
    AWOUTERS, F
    NIEMEGEERS, CJE
    VANDENBUSSCHE, G
    [J]. DRUG DEVELOPMENT RESEARCH, 1986, 8 (1-4) : 27 - 36
  • [4] JANSSENS MML, 1993, CLIN REV ALLERG, V11, P35
  • [5] Risks of non-sedating antihistamines
    Lindquist, M
    Edwards, IR
    [J]. LANCET, 1997, 349 (9061) : 1322 - 1322
  • [6] ASTEMIZOLE - A REVIEW OF ITS PHARMACODYNAMIC PROPERTIES AND THERAPEUTIC EFFICACY
    RICHARDS, DM
    BROGDEN, RN
    HEEL, RC
    SPEIGHT, TM
    AVERY, GS
    [J]. DRUGS, 1984, 28 (01) : 38 - 61
  • [7] β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
    Rothstein, JD
    Patel, S
    Regan, MR
    Haenggeli, C
    Huang, YH
    Bergles, DE
    Jin, L
    Hoberg, MD
    Vidensky, S
    Chung, DS
    Toan, SV
    Bruijn, LI
    Su, ZZ
    Gupta, P
    Fisher, PB
    [J]. NATURE, 2005, 433 (7021) : 73 - 77
  • [8] INHIBITION BY CHLOROQUINE OF A NOVEL HEME POLYMERASE ENZYME-ACTIVITY IN MALARIA TROPHOZOITES
    SLATER, AFG
    CERAMI, A
    [J]. NATURE, 1992, 355 (6356) : 167 - 169
  • [9] Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells
    Traebert, M
    Dumotier, B
    Meister, L
    Hoffmann, P
    Dominguez-Estevez, M
    Suter, W
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 484 (01) : 41 - 48
  • [10] Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs
    Zhou, SF
    Chan, SY
    Goh, BC
    Chan, E
    Duan, W
    Huang, M
    McLeod, HL
    [J]. CLINICAL PHARMACOKINETICS, 2005, 44 (03) : 279 - 304
1