Sign in to NCBI

Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
    J Med Chem. 2004 Aug 26;47(18):4494-506.

    Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors.

    Gellibert F, Woolven J, Fouchet MH, Mathews N, Goodland H, Lovegrove V, Laroze A, Nguyen VL, Sautet S, Wang R, Janson C, Smith W, Krysa G, Boullay V, De Gouville AC, Huet S, Hartley D.

    Source

    Department of Medicinal Chemistry, GlaxoSmithKline, 25-27 Avenue du Québec, 91951 Les Ulis, France. fjg23217@gsk.com

    Abstract

    Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.

    PMID:
    15317461
    [PubMed - indexed for MEDLINE]

    MeSH Terms, Substances, Secondary Source ID

    MeSH Terms

    Substances

    Secondary Source ID

    LinkOut - more resources

    Full Text Sources

    Chemical Information

    Miscellaneous

      Supplemental Content

      Icon for American Chemical Society

      Save items

      loading

      Related citations in PubMed

      See reviews... See all...

      Cited by 7 PubMed Central articles

      See all...

      Structures reported by this article

      Related information

      • Related Citations
        Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
      • BioAssay
        PubChem BioAssay experiments on the biological activities of small molecules that cite the current articles. The depositors of BioAssay data provide these references.
      • Compound
        PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
      • Gene
        Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
      • HomoloGene
        HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
      • Nucleotide (RefSeq)
        NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Nucleotide (Weighted)
        Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
      • Protein (RefSeq)
        NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Protein (Weighted)
        Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
      • Substance
        PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.
      • Substance (MeSH Keyword)
        PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Taxonomy via GenBank
        Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
      • UniGene
        UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
      • Protein
        Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
      • Structure
        Three-dimensional structure records in the NCBI Structure database for data reported in the current articles.
      • GEO Profiles
        Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
      • Cited in PMC
        Full-text articles in the PubMed Central Database that cite the current articles.

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      You are here: NCBI > Literature > PubMed
      Write to the Help Desk