57
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      The promise and peril of chemical probes

      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,   , , , , , , , , , , , , , , , , ,
      Nature Chemical Biology
      Springer Science and Business Media LLC

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          Specificity and mechanism of action of some commonly used protein kinase inhibitors.

          The specificities of 28 commercially available compounds reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases have been examined against a large panel of protein kinases. The compounds KT 5720, Rottlerin and quercetin were found to inhibit many protein kinases, sometimes much more potently than their presumed targets, and conclusions drawn from their use in cell-based experiments are likely to be erroneous. Ro 318220 and related bisindoylmaleimides, as well as H89, HA1077 and Y 27632, were more selective inhibitors, but still inhibited two or more protein kinases with similar potency. LY 294002 was found to inhibit casein kinase-2 with similar potency to phosphoinositide (phosphatidylinositol) 3-kinase. The compounds with the most impressive selectivity profiles were KN62, PD 98059, U0126, PD 184352, rapamycin, wortmannin, SB 203580 and SB 202190. U0126 and PD 184352, like PD 98059, were found to block the mitogen-activated protein kinase (MAPK) cascade in cell-based assays by preventing the activation of MAPK kinase (MKK1), and not by inhibiting MKK1 activity directly. Apart from rapamycin and PD 184352, even the most selective inhibitors affected at least one additional protein kinase. Our results demonstrate that the specificities of protein kinase inhibitors cannot be assessed simply by studying their effect on kinases that are closely related in primary structure. We propose guidelines for the use of protein kinase inhibitors in cell-based assays.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Chemistry: Chemical con artists foil drug discovery.

              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Click chemistry for drug development and diverse chemical-biology applications.

                Bookmark

                Author and article information

                Journal
                Nature Chemical Biology
                Nat Chem Biol
                Springer Science and Business Media LLC
                1552-4450
                1552-4469
                August 2015
                July 21 2015
                August 2015
                : 11
                : 8
                : 536-541
                Article
                10.1038/nchembio.1867
                26196764
                f5eaa605-1d18-4382-86ab-1e90c94634af
                © 2015

                http://www.springer.com/tdm

                History

                Comments

                Comment on this article