Abstract：
:Kinase inhibitors have already established a foothold in the current armament for the treatment of malignancies. Indeed, the future of cancer therapy is likely to rely heavily on an ever-growing number of kinase inhibitors, either as single-agents or in combination with other targeted drugs or even chemotherapies. The progress of the past decade has been driven increasingly by improvements in an integrated drug discovery paradigm that starts with smaller molecular starting points, termed scaffolds, and incorporates X-ray crystallography at the outset of the project. Guided throughout by structural information, the medicinal chemistry efforts are streamlined and enhanced. Here, we review such a paradigm termed scaffold-based design and show how implementation of these methods results in novel, potent, and specific drug candidates.
journal_name
Curr Opin Genet Devjournal_title
Current opinion in genetics & developmentauthors
Zhang C,Bollag Gdoi
10.1016/j.gde.2009.10.010subject
Has Abstractpub_date
2010-02-01 00:00:00pages
79-86issue
1eissn
0959-437Xissn
1879-0380pii
S0959-437X(09)00169-5journal_volume
20pub_type
杂志文章,评审abstract：:The conserved homeobox (Hox) gene cluster is neither conserved nor clustered in the nematode Caenorhabditis elegans. Instead, C. elegans has a reduced and dispersed gene complement that is the result the loss of Hox genes in stages throughout its evolutionary history. The roles of Hox genes in patterning the nematode ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2003.10.009
更新日期：2003-12-01 00:00:00
abstract：:Logical models provide insight about key control elements of biological networks. Based solely on the logical structure, we can determine state transition diagrams that give the allowed possible transitions in a coarse grained phase space. Attracting pathways and stable nodes in the state transition diagram correspond...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.09.005
更新日期：2010-12-01 00:00:00
abstract：:The ability to reprogram cell lineage specification through the activity of master regulatory transcription factors has transformed disease modeling, drug screening, and cell therapy for regenerative medicine. Recent advances in the engineering of synthetic transcription factors to modulate endogenous gene expression ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2018.05.001
更新日期：2018-10-01 00:00:00
abstract：:Long non-coding RNAs (ncRNAs) are emerging as important regulatory factors in mammalian genomics. A number of reports within the last 2 years have identified thousands of actively expressed long ncRNA transcripts with distinct properties. The long ncRNAs show differential expression patterns and regulation in a wide v...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2011.01.020
更新日期：2011-04-01 00:00:00
abstract：:Molecular biological techniques have contributed greatly to the study of vertebrate ocular tissues. The specification of ocular tissues has been shown to be closely related to the expression of transcription factors encoded by genes such as Pax6 and microphthalmia. Lens-specific expression of the delta 1-crystallin ge...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(94)90137-r
更新日期：1994-10-01 00:00:00
abstract：:Premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 gene (FMR1) are known to contribute to the fragile X phenotype through genetic instability and transmission of full mutation alleles (>200 repeats). There is now mounting evidence that the premutation alleles themselves contribute to clinic...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(02)00299-x
更新日期：2002-06-01 00:00:00
abstract：:Unexpected relationships among the various aminoacyl-tRNA synthetases continue to be uncovered. The question arises - is this mainly the result of promiscuous exchange, or is the confusion really a reflection of the differential loss of past duplications? Phylogenetic analysis may yet provide the answer. ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(98)80030-0
更新日期：1998-12-01 00:00:00
abstract：:Recent reprogramming studies indicate that mammalian, somatic cells have the potential to achieve pluripotent states and undergo cell type switching. Such cellular traits are observed under natural conditions in animals that regenerate complex organs. A number of invertebrates display the amazing trait of whole body r...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2012.09.006
更新日期：2012-10-01 00:00:00
abstract：:In eukaryotes, the genetic material is stored in the nucleus, which is enclosed in a double lipid bilayer, the nuclear envelope (NE). It protects the genome from physical stress and separates it from the rest of the cell. On top of this physical function, growing evidence shows that the nuclear periphery contributes t...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2012.12.001
更新日期：2013-04-01 00:00:00
abstract：:Recognition and pairing of homologous chromosomes are absolutely required for successful segregation during meiosis. We still have no model, however, that adequately explains the mechanism of these processes in a quantitative way. The fact that homologue pairing takes similar times across several orders of magnitude i...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2009.02.006
更新日期：2009-04-01 00:00:00
abstract：:TGFβ acts as a potent tumor suppressor and tumor promoter in a context dependent manner. Tumor suppressive functions include inhibition of cell proliferation, induction of apoptosis and regulation of autophagy. As tumors develop they switch their response to TGFβ and utilise this factor as a potent promoter of cell mo...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.12.004
更新日期：2011-02-01 00:00:00
abstract：:Dramatic genome rearrangement has been observed after whole genome duplication (WGD) in some plant species, leading many to suggest that genome restructuring may be a common consequence of WGD. However, recent analyses of ancient WGDs in yeast and vertebrates have not shown any evidence for increased rearrangement aft...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2009.10.005
更新日期：2009-12-01 00:00:00
abstract：:Mitochondria are highly abundant in and essential to the beat-to-beat contractile performance of hearts. However, relatively few cardiac diseases have been attributed to primary mitochondrial dysfunction. The paucity of evidence for 'primary mitochondrial cardiac diseases' may be because such an entity does not exist....
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2016.03.001
更新日期：2016-06-01 00:00:00
abstract：:The computational properties of intracellular biochemical networks, for which the cell is assumed to be a 'well-mixed' reactor, have already been widely characterized. What has so far not received systematic treatment is the important role of space in many intracellular computations. Spatial network computations can b...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2009.12.006
更新日期：2010-02-01 00:00:00
abstract：:Multiple neural and non-neural cell types arise from the neural crest (NC) in vertebrate embryos. Recent work has provided evidence for multipotent stem cells and intermediate precursors in the early NC cell population as well as in various NC derivatives in embryos and even in adult. Advances have been made towards u...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2003.08.002
更新日期：2003-10-01 00:00:00
abstract：:The advent of the genomics age has greatly facilitated the study of crop evolution. While full-scale genome sequencing projects are underway for just a handful of crop plants, recent years have witnessed a tremendous increase in the availability of DNA sequence data for virtually all major crops. Such resources have b...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2007.09.003
更新日期：2007-12-01 00:00:00
abstract：:The genomic variability of Southern African groups is characterized by an exceptional degree of diversity, which is the result of long-term local evolutionary history, migrations and gene-flow. Over the last few years several investigations have identified and described signatures related to these processes, revealing...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2018.11.003
更新日期：2018-12-01 00:00:00
abstract：:New structural studies of RNA polymerase II (Pol II) complexes mark the beginning of a detailed mechanistic analysis of the eukaryotic mRNA transcription cycle. Crystallographic models of the complete Pol II, together with new biochemical and electron microscopic data, give insights into transcription initiation. The ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2004.01.003
更新日期：2004-04-01 00:00:00
abstract：:Cellular fate reprogramming holds great promise to generate functional cell types for replenishing new cells and restoring functional loss. Inspired by transcription factor-induced reprogramming, the field of cellular reprogramming has greatly advanced and developed into divergent streams of reprogramming approaches. ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2018.05.004
更新日期：2018-10-01 00:00:00
abstract：:The regulation of synapse formation and plasticity in the developing and adult brain underlies a complex interplay of intrinsic genetic programs and extrinsic factors. Recent research identified microRNAs (miRNAs), a class of small non-coding RNAs, as a new functional layer in this regulatory network. Within only a fe...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2011.04.008
更新日期：2011-08-01 00:00:00
abstract：:Population data suggest that many parasitic protozoa (e.g. Trypanosoma, Leishmania, Entamoeba and Giardia) reproduce clonally, but this hypothesis has been highly controversial for Plasmodium falciparum. Although reproduction is predominantly clonal in the enteric bacteria Escherichia coli and Salmonella, the level of...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(05)80119-4
更新日期：1992-12-01 00:00:00
abstract：:The circadian clock of the cyanobacterium Synechococcus elongatus PCC 7942 is built on a three-protein central oscillator that can be reconstituted in vitro, a redox-sensitive input for synchronization with the environment, and a bacterial two-component signal transduction pathway for global transcriptional regulation...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.09.002
更新日期：2010-12-01 00:00:00
abstract：:Bladder cancer is the 5th commonest cancer and two major risk factors are smoking and occupational chemical exposure. There is also evidence of a genetic component to its aetiology. Candidate gene studies have mostly focused on genes involved in adduct metabolism and DNA repair, including a recent consortium-based met...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.01.002
更新日期：2010-06-01 00:00:00
abstract：:Hepatocytes differentiate from the endoderm during embryonic development. Recent studies show, however, that hepatocytes can also be derived from rare cells that reside in the pancreas, bone marrow, and brain. Indeed, the latest discoveries indicate that embryonic hepatocytes normally arise by diversion of an endoderm...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(00)00234-3
更新日期：2001-10-01 00:00:00
abstract：:The maternal-to-zygotic transition (MZT) is a universal step in animal development characterized by two major events: activation of zygotic transcription and degradation of maternally provided mRNAs. How zygotic gene products instruct the degradation of maternal messages remains a long-standing question in biology. Mi...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.04.003
更新日期：2010-08-01 00:00:00
abstract：:Cell-cell and starvation signals are funneled through the phosphorelay to initiate sporulation by activating the transcription regulator SpoOA. Activation of SpoOA leads to synthesis of the transcription factors sigmaF and sigmaE. Substantial advances have been made in our understanding of the signal circuitry of the ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(96)80080-3
更新日期：1996-10-01 00:00:00
abstract：:Cardiovascular morphogenesis involves cell behavior and cell identity changes that are activated by mechanical forces associated with heart function. Recently, advances in in vivo imaging, methods to alter blood flow, and computational modelling have greatly advanced our understanding of how forces produced by heart c...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2019.08.002
更新日期：2019-08-01 00:00:00
abstract：:Subtelomeres are the regions at chromosome ends, immediately adjacent to the terminal telomeric repeats. The majority of human subtelomeres are CpG-rich in their distal two kilobases, and are methylated during early embryonic development by the de novo DNA methyltransferase DNMT3B. The biological relevance of subtelom...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2020.02.004
更新日期：2020-02-01 00:00:00
abstract：:Mutant onco-proteins play a direct, causal role in cancer and are therefore considered attractive drug targets. Clinical experience has supported this view, with some exceptions. However, clinical benefit has often been restricted by rapid emergence of drug-resistant clones through several distinct mechanisms. This pr...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.12.002
更新日期：2011-02-01 00:00:00
abstract：:The induction of apoptosis of virus-infected cells is an important host defense mechanism against invading pathogens. Some viruses express anti-apoptotic proteins that efficiently block apoptosis induced by death receptors or in response to stress signaled through mitochondria. Viral interference with host cell apopto...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(98)80066-x
更新日期：1998-02-01 00:00:00
