17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      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.

          Abstract

          This article provides an overview of approximately 300 secondary metabolites with inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), which were isolated from various natural sources or derived from synthetic process in the last decades. The structure-activity relationship and the selectivity of some compounds against other protein phosphatases were also discussed. Potential pharmaceutical applications of several PTP1B inhibitors were presented.

          Related collections

          Most cited references189

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

          PTP1B as a drug target: recent developments in PTP1B inhibitor discovery.

          Protein tyrosine phosphatase 1B (PTP1B) is an effective target for the treatment of both type 2 diabetes and obesity; however, targeting PTP1B for drug discovery is challenging because of the highly conserved and positively charged active-site pocket. Tremendous progress has been made in the development of potent and selective PTP1B inhibitors that engage both the active site and no catalytic sites. Several strategies are being pursued to improve the pharmacological properties of PTP1B inhibitors. These new developments suggest that it is feasible to acquire PTP1B-based, small-molecule therapeutics with the requisite potency and selectivity. Future efforts will probably transform the potent and selective PTP1B inhibitors into orally available drugs with desirable physicochemical properties and in vivo efficacies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism.

            Our previous studies have clearly shown that the angiogenic enzymes, matrix metalloproteinase (MMP) -2/9, are directly involved in human hepatic tumorigenesis and metastasis and suggest that the MMP-2/9 inhibitors, which have dual inhibitory activities on enzyme activity and transcription, represent the best candidates for achieving tumor regression. Many anti-cancer drugs have strong cellular cytotoxicity and side effects, indicating that strong anti-cancer drugs that have no or minimal cytotoxicity and side effects need to be developed. The specific aim of the present study was to develop powerful anti-cancer drugs with specific tumor regression and anti-metastatic potential having the dual inhibitory activities of specific MMP-2 and -9 enzyme activities and gene transcription at the molecular level. Caffeic acid (CA), a strong and selective MMP-9 activity and transcription inhibitor, was isolated from the plant Euonymus alatus and its derivative, caffeic acid phenethyl ester (CAPE), was synthesized. CA and CAPE selectively inhibited MMP-2 and -9 but not -1, -3, -7, or cathepsin K. Treatment of HepG2 cells with CA (100 microg/mL) and CAPE (5 microg/mL) suppressed phorbol 12-myristate 13-acetate (PMA) -induced MMP-9 expression by inhibiting the function of NF-kappaB, but not AP-1. We confirmed that CA and CAPE suppressed the growth of HepG2 tumor xenografts in nude mice in vivo. The subcutaneous and oral administrations of CA and CAPE significantly reduced the liver metastasis. These results confirm the therapeutic potential of the compounds and suggest that the anti-metastatic and anti-tumor effects of CA and CAPE are mediated through the selective suppression of MMP-9 enzyme activity and transcriptional down-regulation by the dual inhibition of NF-kappaB as well as MMP-9 catalytic activity.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Diversity in lignan biosynthesis

                Bookmark

                Author and article information

                Journal
                Acta Pharmacol Sin
                Acta Pharmacol. Sin
                Acta Pharmacologica Sinica
                Nature Publishing Group
                1671-4083
                1745-7254
                October 2012
                03 September 2012
                : 33
                : 10
                : 1217-1245
                Affiliations
                [1 ]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China
                Author notes
                [#]

                These two authors contributed equally to this article.

                Article
                aps201290
                10.1038/aps.2012.90
                4002712
                22941286
                bbb0d641-efbd-4f94-b99c-5ce4fd7bdcf5
                Copyright © 2012 CPS and SIMM
                History
                : 16 February 2012
                : 08 June 2012
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                natural products,phytochemistry,protein tyrosine phosphatase 1b (ptp1b),inhibitor,structure-activity relationship (sar),type 2 diabetes,obesity

                Comments

                Comment on this article