A small-molecule antagonist of the hedgehog signaling pathway

被引：68
作者：
Lee, Jongkook
Wu, Xu
di Magliano, Marina Pasca
Peters, Eric C.
Wang, Yan
Hong, Jiyong
Hebrok, Metthias
Din, Sheng
Cho, Charles Y.
Schultz, Peter G.
机构：
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA
[4] Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94143 USA
来源：
CHEMBIOCHEM | 2007年 / 8卷 / 16期
关键词：
D O I：
10.1002/cbic.200700403
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：
Shadow the Hedgehog. JK184 (illustrated in the scheme) was identified as an antagonist of Hedgehog signaling through a cell-based screen of chemical libraries. Results from biochemical and cellular experiments suggest that JK1 84 functions by inhibiting class IV alcohol dehydrogenase. This molecule should serve as a useful tool for studying Hedgehog signaling.
引用
收藏
页码：1916 / +
页数：5
相关论文
共 30 条
  • [1] Retinoids, ω-hydroxyfatty acids and cytotoxic aldehydes as physiological substrates, and H2-receptor antagonists as pharmacological inhibitors, of human class IV alcohol dehydrogenase
    Allali-Hassani, A
    Peralba, JM
    Martras, S
    Farrés, J
    Parés, X
    [J]. FEBS LETTERS, 1998, 426 (03) : 362 - 366
  • [2] Retinoic acid synthesis in mouse embryos during gastrulation and craniofacial development linked to class IV alcohol dehydrogenase gene expression
    Ang, HL
    Deltour, L
    Hayamizu, TF
    ZgombicKnight, M
    Duester, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (16) : 9526 - 9534
  • [3] Tissue repair and stem cell renewal in carcinogenesis
    Beachy, PA
    Karhadkar, SS
    Berman, DM
    [J]. NATURE, 2004, 432 (7015) : 324 - 331
  • [4] BEACHY PA, Patent No. 2005033288
  • [5] Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened
    Chen, JK
    Taipale, J
    Cooper, MK
    Beachy, PA
    [J]. GENES & DEVELOPMENT, 2002, 16 (21) : 2743 - 2748
  • [6] Small molecule modulation of Smoothened activity
    Chen, JK
    Taipale, J
    Young, KE
    Maiti, T
    Beachy, PA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) : 14071 - 14076
  • [7] Teratogen-mediated inhibition of target tissue response to Shh signaling
    Cooper, MK
    Porter, JA
    Young, KE
    Beachy, PA
    [J]. SCIENCE, 1998, 280 (5369) : 1603 - 1607
  • [8] Chemical genetics: exploring and controlling cellular processes with chemical probes
    Crews, CM
    Splittgerber, U
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (08) : 317 - 320
  • [9] Hedgehog signalling in cancer formation and maintenance
    di Magliano, MP
    Hebrok, M
    [J]. NATURE REVIEWS CANCER, 2003, 3 (12) : 903 - 911
  • [10] A role for chemistry in stem cell biology
    Ding, S
    Schultz, PG
    [J]. NATURE BIOTECHNOLOGY, 2004, 22 (07) : 833 - 840
123