Abstract:
:There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.
journal_name
Naturejournal_title
Natureauthors
Baragaña B,Hallyburton I,Lee MC,Norcross NR,Grimaldi R,Otto TD,Proto WR,Blagborough AM,Meister S,Wirjanata G,Ruecker A,Upton LM,Abraham TS,Almeida MJ,Pradhan A,Porzelle A,Luksch T,Martínez MS,Luksch T,Bolscher JM,doi
10.1038/nature14451subject
Has Abstractpub_date
2015-06-18 00:00:00pages
315-20issue
7556eissn
0028-0836issn
1476-4687pii
nature14451journal_volume
522pub_type
杂志文章相关文献
NATURE文献大全abstract::In this Article, in Fig. 1a, the 5' and 3' labels were reversed in the DNA sequence, and Fig. 4 was missing panel labels a-e. These errors have been corrected online. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-019-1343-8
更新日期:2019-07-01 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/d41586-018-07692-4
更新日期:2018-12-01 00:00:00
abstract::Nerve growth factor (NGF) activity was not detected by bioassay in irides killed immediately after excision but NGF appeared within 24 h in living irides placed in culture or grafted to a host eye. Furthermore, sensory and, although less effective, sympathetic denervation of irides in situ led within 10 days to the ap...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/286025a0
更新日期:1980-07-03 00:00:00
abstract::The mir-34/449 family consists of six homologous miRNAs at three genomic loci. Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated epithelia suggest a functional significance in ciliogenesis. Here we report that mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality, infertil...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13413
更新日期:2014-06-05 00:00:00
abstract::Sounds heard over headphones are typically perceived inside the head (internalized), unlike real sound sources which are perceived outside the head (externalized). If the acoustical waveforms from a real sound source are reproduced precisely using headphones, auditory images are appropriately externalized and localize...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/25526
更新日期:1998-12-24 00:00:00
abstract::Braunwald, a professor at Harvard Medical School, responds to a paper by Walter W. Stewart and Ned Feder ("The integrity of the scientific literature," Nature 1987 Jan 15; 325(6101): 207-214) concerning their findings of errors, discrepancies, and other lapses in publications coauthored by John Darsee, a biomedical re...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/325215a0
更新日期:1987-01-15 00:00:00
abstract::Sex in mammals is determined in the fetal gonad by the presence or absence of the Y chromosome gene Sry, which controls whether bipotential precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells. This pivotal decision in a single gonadal cell type ultimately controls sexual differentiat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10239
更新日期:2011-07-20 00:00:00
abstract::The variable (V) regions of heavy and light immunoglobulin chains are encoded by multiple germline DNA elements which are assembled into complete variable-region genes in precursor(pre-) B lymphocytes. The heavy-chain V region (VH) is assembled from three separate germline DNA elements, the variable (VH), diversity (D...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317353a0
更新日期:1985-09-26 00:00:00
abstract::Change history: In this Letter, the received date should be 20 December 2017, instead of 27 April 2018. This has been corrected online. ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41586-018-0314-9
更新日期:2018-10-01 00:00:00
abstract::Susceptibility to some human diseases is linked, albeit weakly, to major transplantation antigens (HLA) encoded by the major histocompatibility gene complex (MHC). Here we have studied MHC/disease association in inbred strains of mice after intracerebral (i.c.) injection of lymphocytic choriomeningitis virus (LCMV). T...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/316814a0
更新日期:1985-08-29 00:00:00
abstract::Chondrules are millimetre-sized spherules (mostly silicate) that dominate the texture of primitive meteorites. Their formation mechanism is debated, but their sheer abundance suggests that the mechanism was both energetic and ubiquitous in the early inner Solar System. The processes suggested--such as shock waves, sol...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04834
更新日期:2006-05-25 00:00:00
abstract::The mechanism whereby eukaryotic pre-messenger RNAs are polyadenylated is unknown. Most models for polyadenylation invoke cleavage of precursor transcripts at the site of poly(A) addition followed by polymerization of A residues by poly(A) polymerase. Analysis of the sequences surrounding poly(A) addition sites has id...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/309179a0
更新日期:1984-05-10 00:00:00
abstract::The mobilization of aluminium from acidic forest soils is arguably the most ecologically important consequence of acid deposition in the environment because of its adverse effects on soils, forest vegetation and surface water. Here we show that there has been a significant decline in the concentrations of aluminium sp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/417242a
更新日期:2002-05-16 00:00:00
abstract::Theory predicts that sexual behaviour in animals can evolve rapidly, accelerating the rate of species formation. Here we estimate the rate of speciation in Laupala, a group of forest-dwelling Hawaiian crickets that is characterized primarily through differences in male courtship song. We find that Laupala has the high...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/433375a
更新日期:2005-01-27 00:00:00
abstract::Jupiter's atmosphere is rotating differentially, with zones and belts rotating at speeds that differ by up to 100 metres per second. Whether this is also true of the gas giant's interior has been unknown, limiting our ability to probe the structure and composition of the planet. The discovery by the Juno spacecraft th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25775
更新日期:2018-03-07 00:00:00
abstract::Early observations indicated that the Earth's Van Allen radiation belts could be separated into an inner zone dominated by high-energy protons and an outer zone dominated by high-energy electrons. Subsequent studies showed that electrons of moderate energy (less than about one megaelectronvolt) often populate both zon...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13956
更新日期:2014-11-27 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07667-5
更新日期:2018-12-01 00:00:00
abstract::Anterior-posterior patterning in insects, vertebrates and nematodes involves members of conserved Antennapedia-class homeobox gene clusters (HOM-C) that are thought to give specific body regions their identities. The effects of these genes on region-specific body structures have been described extensively, particularl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/355255a0
更新日期:1992-01-16 00:00:00
abstract::Several microorganisms, including Yersinia sp., Salmonella sp., Brucella sp., Mycobacterium sp. and Leishmania sp., have successfully adapted to grow within macrophage phagolysosomes. Infections caused by these intracellular pathogens are among the most difficult to treat. As part of an antimicrobial strategy directed...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/322834a0
更新日期:1986-08-28 00:00:00
abstract::Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/346183a0
更新日期:1990-07-12 00:00:00
abstract::Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10639
更新日期:2011-11-02 00:00:00
abstract::A key step in the elimination of pathogens from the body is the covalent binding of complement proteins C3 and C4 to their surfaces. Proteolytic activation of these proteins results in a conformational change, and an internal thioester is exposed which reacts with amino or hydroxyl groups on the target surface to form...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/379177a0
更新日期:1996-01-11 00:00:00
abstract::Protonic ceramic fuel cells, like their higher-temperature solid-oxide fuel cell counterparts, can directly use both hydrogen and hydrocarbon fuels to produce electricity at potentially more than 50 per cent efficiency1,2. Most previous direct-hydrocarbon fuel cell research has focused on solid-oxide fuel cells based ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0082-6
更新日期:2018-05-01 00:00:00
abstract::In songbirds, the remarkable temporal precision of song is generated by a sparse sequence of bursts in the premotor nucleus HVC. To distinguish between two possible classes of models of neural sequence generation, we carried out intracellular recordings of HVC neurons in singing zebra finches (Taeniopygia guttata). We...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09514
更新日期:2010-11-18 00:00:00
abstract::Multicomponent reactions are relied on in both academic and industrial synthetic organic chemistry owing to their step- and atom-economy advantages over traditional synthetic sequences1. Recently, bicyclo[1.1.1]pentane (BCP) motifs have become valuable as pharmaceutical bioisosteres of benzene rings, and in particular...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2060-z
更新日期:2020-04-01 00:00:00
abstract::Genetic studies, using floral homeotic mutants, have led to the ABC model of flower development. This model proposes that the combinatorial action of three sets of genes, the A, B and C function genes, specify the four floral organs (sepals, petals, stamens and carpels) in the concentric floral whorls. However, attemp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35054083
更新日期:2001-01-25 00:00:00
abstract::A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three am...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2228-6
更新日期:2020-06-01 00:00:00
abstract::In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11739
更新日期:2012-12-20 00:00:00
abstract::Spin dynamics in antiferromagnets has much shorter timescales than in ferromagnets, offering attractive properties for potential applications in ultrafast devices1-3. However, spin-current generation via antiferromagnetic resonance and simultaneous electrical detection by the inverse spin Hall effect in heavy metals h...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-1950-4
更新日期:2020-02-01 00:00:00
abstract::Cells sense the context in which they grow to adapt their phenotype and allow multicellular patterning by mechanisms of autocrine and paracrine signalling. However, patterns also form in cell populations exposed to the same signalling molecules and substratum, which often correlate with specific features of the popula...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14429
更新日期:2015-07-02 00:00:00