L Meijer

Summary

Affiliation: Station Biologique
Country: France

Publications

  1. pmc Soluble 3',6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period
    Konstantina Vougogiannopoulou
    Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771 Athens, Greece
    J Med Chem 51:6421-31. 2008
  2. ncbi request reprint Intracellular Targets of Paullones. Identification following affinity purification on immobilized inhibitor
    Marie Knockaert
    Station Biologique de Roscoff, CNRS, BP 74, Bretagne, France
    J Biol Chem 277:25493-501. 2002
  3. ncbi request reprint Pharmacological inhibitors of glycogen synthase kinase 3
    Laurent Meijer
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021 6399, USA
    Trends Pharmacol Sci 25:471-80. 2004
  4. pmc Anticancer alkaloid lamellarins inhibit protein kinases
    Dianne Baunbaek
    C N R S, Cell Cycle Group, Station Biologique, Bretagne, France
    Mar Drugs 6:514-27. 2008
  5. ncbi request reprint Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent
    L Meijer
    CNRS, Station Biologique, Roscoff Cedex, 29682, France
    Chem Biol 7:51-63. 2000
  6. ncbi request reprint Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
  7. ncbi request reprint GSK-3-selective inhibitors derived from Tyrian purple indirubins
    Laurent Meijer
    CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Chem Biol 10:1255-66. 2003
  8. ncbi request reprint Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors?
    S Leclerc
    CNRS, Cell Cycle Group, Station Biologique, BP 74, Roscoff 29682 Cedex, Bretagne, France
    J Biol Chem 276:251-60. 2001
  9. ncbi request reprint Sequential dephosphorylation of p34(cdc2) on Thr-14 and Tyr-15 at the prophase/metaphase transition
    A Borgne
    Centre National de la Recherche Scientifique, Station Biologique, BP 74, 29682 Roscoff Cedex, France
    J Biol Chem 271:27847-54. 1996
  10. ncbi request reprint Screening for antimitotic compounds using the cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2/cyclin Bcdc13 protein kinase
    B Baratte
    CNRS, Station Biologique, Roscoff, France
    Anticancer Res 12:873-80. 1992

Detail Information

Publications87

  1. pmc Soluble 3',6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period
    Konstantina Vougogiannopoulou
    Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771 Athens, Greece
    J Med Chem 51:6421-31. 2008
    ..The new indirubins inhibit GSK-3 in a cellular reporter model. They alter the circadian period measured in rhythmically expressing cell cultures, suggesting that they might constitute tools to investigate circadian rhythm regulation...
  2. ncbi request reprint Intracellular Targets of Paullones. Identification following affinity purification on immobilized inhibitor
    Marie Knockaert
    Station Biologique de Roscoff, CNRS, BP 74, Bretagne, France
    J Biol Chem 277:25493-501. 2002
    ..It has revealed an unexpected target, mitochondrial MDH, the inhibition of which may participate in the pharmacological effects of paullones...
  3. ncbi request reprint Pharmacological inhibitors of glycogen synthase kinase 3
    Laurent Meijer
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021 6399, USA
    Trends Pharmacol Sci 25:471-80. 2004
    ..GSK-3, as part of a multi-protein complex that contains proteins such as axin, presenilin and beta-catenin, contains many additional target sites for specific modulation of its activity...
  4. pmc Anticancer alkaloid lamellarins inhibit protein kinases
    Dianne Baunbaek
    C N R S, Cell Cycle Group, Station Biologique, Bretagne, France
    Mar Drugs 6:514-27. 2008
    ..Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors...
  5. ncbi request reprint Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent
    L Meijer
    CNRS, Station Biologique, Roscoff Cedex, 29682, France
    Chem Biol 7:51-63. 2000
    ..Over 2000 protein kinases regulate cellular functions. Screening for inhibitors of some of these kinases has already yielded some potent and selective compounds with promising potential for the treatment of human diseases...
  6. ncbi request reprint Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
    ..Through its unique selectivity for some cyclin-dependent kinases, roscovitine provides a useful antimitotic reagent for cell cycle studies and may prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase activities...
  7. ncbi request reprint GSK-3-selective inhibitors derived from Tyrian purple indirubins
    Laurent Meijer
    CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Chem Biol 10:1255-66. 2003
    ..BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3...
  8. ncbi request reprint Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors?
    S Leclerc
    CNRS, Cell Cycle Group, Station Biologique, BP 74, Roscoff 29682 Cedex, Bretagne, France
    J Biol Chem 276:251-60. 2001
    ..Indirubins constitute the first family of low nanomolar inhibitors of GSK-3 beta to be described...
  9. ncbi request reprint Sequential dephosphorylation of p34(cdc2) on Thr-14 and Tyr-15 at the prophase/metaphase transition
    A Borgne
    Centre National de la Recherche Scientifique, Station Biologique, BP 74, 29682 Roscoff Cedex, France
    J Biol Chem 271:27847-54. 1996
    ....
  10. ncbi request reprint Screening for antimitotic compounds using the cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2/cyclin Bcdc13 protein kinase
    B Baratte
    CNRS, Station Biologique, Roscoff, France
    Anticancer Res 12:873-80. 1992
    ..The simplicity, speed and possible extensive automation of this assay using an essential cell cycle-regulating component provide a highly specific mechanism-based screen for antimitotic drugs discovery...
  11. ncbi request reprint 7-Bromoindirubin-3'-oxime induces caspase-independent cell death
    J Ribas
    CNRS, Cell Cycle Group and UPS2682, Station Biologique, Bretagne, France
    Oncogene 25:6304-18. 2006
    ..Although their molecular targets remain to be identified, 7-substituted indirubins may constitute a new class of potential antitumor compounds that would retain their activity in cells refractory to apoptosis...
  12. doi request reprint CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases
    K Bettayeb
    CNRS, Cell Cycle Group, Station Biologique, Bretagne, France
    Oncogene 27:5797-807. 2008
    ..Altogether these results show that second-generation analogues of (R)-roscovitine can be designed with improved antitumor potential...
  13. ncbi request reprint Anti-mitotic properties of indirubin-3'-monoxime, a CDK/GSK-3 inhibitor: induction of endoreplication following prophase arrest
    E Damiens
    CNRS, Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff Cedex, Bretagne, France
    Oncogene 20:3786-97. 2001
    ..As soon as indirubin-3'-monoxime is washed away, these polyploid cells become aneuploid and later die from necrosis. This mechanism of endoreplication followed by cell death may contribute to the anti-tumour properties of indirubins...
  14. ncbi request reprint [Prevention of chemotherapy-induced alopecia by cyclin-dependant kinase inhibitors]
    L Meijer
    CNRS, Groupe cycle de division cellulaire, Station Biologique, BP 74, 29682 Roscoff Cedex
    Bull Cancer 88:347-50. 2001
    ..These cyto-protective properties might also be extended to other tissues damaged during chemotherapy...
  15. ncbi request reprint Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons
    J A Bibb
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
    Nature 402:669-71. 1999
    ..Thus DARPP-32 is a bifunctional signal transduction molecule which, by distinct mechanisms, controls a serine/threonine kinase and a serine/threonine phosphatase...
  16. ncbi request reprint cdc2 is a component of the M phase-specific histone H1 kinase: evidence for identity with MPF
    D Arion
    CNRS, Roscoff, France
    Cell 55:371-8. 1988
    ..Since this protein is also a subunit of the M-phase promoting factor (MPF) of Xenopus oocytes, we suggest that H1K and MPF are the same entity, and that histone H1 is likely to be one substrate of the pleiotropic MPF...
  17. ncbi request reprint Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor
    Noboru Sato
    Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Nat Med 10:55-63. 2004
    ..These results suggest that the use of GSK-3-specific inhibitors such as BIO may have practical applications in regenerative medicine...
  18. ncbi request reprint Interaction between the cell-cycle-control proteins p34cdc2 and p9CKShs2. Evidence for two cooperative binding domains in p9CKShs2
    L Azzi
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 203:353-60. 1992
    ..The implications of the existence of two cooperative p34cdc2-binding domains in p9CKShs2 on the structure of the active M-phase-specific kinase is discussed...
  19. ncbi request reprint CDK1/cyclin B regulation during oocyte maturation in two closely related lugworm species, Arenicola marina and Arenicola defodiens
    Fabienne Chausson
    School of Marine Science and Technology, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK
    Dev Growth Differ 46:71-82. 2004
    ....
  20. ncbi request reprint Independent actions on cyclin-dependent kinases and aryl hydrocarbon receptor mediate the antiproliferative effects of indirubins
    Marie Knockaert
    C N R S, Cell Cycle Group and UPS 2682, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Oncogene 23:4400-12. 2004
    ..In contrast, kinase inhibition, rather than AhR activation, represents the main mechanism underlying the cytotoxic properties of this class of promising antitumor molecules...
  21. pmc Degradation of Hof1 by SCF(Grr1) is important for actomyosin contraction during cytokinesis in yeast
    Marc Blondel
    CNRS, Station Biologique, UMR7150, Amyloids and Cell Division Cycle Laboratory, Place G Teissier, Roscoff, Bretagne, France
    EMBO J 24:1440-52. 2005
    ..SCF(Grr1)-mediated degradation of Hof1 may thus represent a novel mechanism to couple exit from mitosis with initiation of cytokinesis...
  22. ncbi request reprint Roscovitine targets, protein kinases and pyridoxal kinase
    Stephane Bach
    CNRS, Cell Cycle Group, UPS 2682 and UMR 2775, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    J Biol Chem 280:31208-19. 2005
    ..These results could help in interpreting the cellular actions of (R)-roscovitine but also in guiding the synthesis of more selective roscovitine analogs...
  23. ncbi request reprint High-mobility-group proteins P1, I and Y as substrates of the M-phase-specific p34cdc2/cyclincdc13 kinase
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 196:557-67. 1991
    ..The phosphorylation of these proteins by p34cdc2/cyclincdc13 may represent a crucial event in the intense chromatin condensation occurring as cells transit from the G2 to the M phase of the cell cycle...
  24. ncbi request reprint CDK/GSK-3 inhibitors as therapeutic agents for parenchymal renal diseases
    S H Obligado
    Division of Nephrology, New York University School of Medicine, New York, New York 10016, USA
    Kidney Int 73:684-90. 2008
    ..Novel biomarkers of therapy are aiding the process of drug development. This review will highlight these advancements in renal therapeutics...
  25. ncbi request reprint p42/p44 MAPKs are intracellular targets of the CDK inhibitor purvalanol
    Marie Knockaert
    Station Biologique de Roscoff, CNRS, B P 74, 29682 Roscoff Cedex, Bretagne, France
    Oncogene 21:6413-24. 2002
    ..These observations highlight the potency of moderate selectivity compounds and encourage the search for new therapeutics which simultaneously target distinct but relevant pathways of cell proliferation...
  26. ncbi request reprint Plasmodium falciparum glycogen synthase kinase-3: molecular model, expression, intracellular localisation and selective inhibitors
    Eliane Droucheau
    C N R S, Cell Cycle Group, Station Biologique, B P 74, 29682 Roscoff Cedex, Bretagne, France
    Biochim Biophys Acta 1697:181-96. 2004
    ..A series of GSK-3 beta inhibitors were tested on both PfGSK-3 and mammalian GSK-3beta. Remarkably these enzymes show a partially divergent sensitivity to the compounds, suggesting that PfGSK-3 selective compounds might be identified...
  27. ncbi request reprint Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation
    Marie Gompel
    CNRS, Cell Cycle Group, Station Biologique, Roscoff, France
    Neurosignals 13:134-43. 2004
    ..Pharmacological inhibitors of CDKs and GSK-3 lead to a dose-dependent decrease in cell viability...
  28. ncbi request reprint Identifying in vivo targets of cyclin-dependent kinase inhibitors by affinity chromatography
    Marie Knockaert
    Station Biologique de Roscoff, C N R S, BP 74, Cell Cycle Group, Place Georges Teissier, Roscoff, France
    Biochem Pharmacol 64:819-25. 2002
    ..In addition to confirming the interaction of CDK inhibitors with CDKs, this method has led to the identification of additional, sometimes unexpected, targets. We here illustrate the potential of this technique through a few examples...
  29. ncbi request reprint 3'-Substituted 7-halogenoindirubins, a new class of cell death inducing agents
    Yoan Ferandin
    Cell Cycle Group and UPS2682, C N R S, Station Biologique, B P 74, 29682 Roscoff Cedex, Bretagne, France
    J Med Chem 49:4638-49. 2006
    ..Despite their unidentified targets, 3'-substituted 7-halogenoindirubins constitute a new promising family of antitumor agents...
  30. doi request reprint Identification of potential cellular targets of aloisine A by affinity chromatography
    Caroline Corbel
    CNRS USR 3151, Protein Phosphorylation and Human Disease, Station Biologique, B P 74, F 29682 Roscoff Cedex, Bretagne, France
    Bioorg Med Chem 17:5572-82. 2009
    ..Affinity chromatography of various biological extracts on the aloisine matrices allowed the identification of both protein kinases and non-kinase proteins as potential cellular targets of aloisine...
  31. ncbi request reprint Meriolins, a new class of cell death inducing kinase inhibitors with enhanced selectivity for cyclin-dependent kinases
    Karima Bettayeb
    Centre National de la Recherche Scientifique, Cell Cycle Group and UPS2682, Station Biologique, Roscoff, Bretagne, France
    Cancer Res 67:8325-34. 2007
    ..Meriolins thus constitute a new CDK inhibitory scaffold, with promising antitumor activity, derived from molecules initially isolated from marine organisms...
  32. ncbi request reprint Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials
    Laurent Meijer
    Station Biologique de Roscoff, C N R S, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Acc Chem Res 36:417-25. 2003
    ....
  33. ncbi request reprint Purine-based inhibitors of inositol-1,4,5-trisphosphate-3-kinase
    Young Tae Chang
    Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA
    Chembiochem 3:897-901. 2002
  34. ncbi request reprint Molecular cloning and characterisation of p15(CDK-BP), a novel CDK-binding protein
    Lee Vogel
    CNRS, Station Biologique, Roscoff, Bretagne, France
    Biochim Biophys Acta 1589:219-31. 2002
    ..In addition p15B interacts tightly with CDK4, CDK6, CDK8 and the yeast CDC28-related kinase Pho85, but not with CDK1, CDK2 or CDK7. P15 does not appear to alter the catalytic activity of the bound kinases...
  35. ncbi request reprint Identification of intracellular targets of small molecular weight chemical compounds using affinity chromatography
    Damien Guiffant
    CNRS, Molecules and Therapeutic Targets Laboratory, Station Biologique, Roscoff, France
    Biotechnol J 2:68-75. 2007
    ..This method not only allows the systematic investigation of the selectivity of pharmacological compounds but also the anticipation of their putative adverse effects...
  36. ncbi request reprint CDK/GSK-3 inhibitors as a new approach for the treatment of proliferative renal diseases
    Timothy J Soos
    Division of Nephrology, New York University School of Medicine, New York, NY 10016, USA
    Drug News Perspect 19:325-8. 2006
    ..Thus, CDK/GSK-3 inhibitors may emerge as effective drugs for proliferative renal diseases due to their integrative properties across several aspects of disease pathogenesis. This brief mini-review will highlight these issues...
  37. ncbi request reprint (R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastoma cells to nutlin-3-induced apoptosis
    Judit Ribas
    CNRS, Cell Cycle Group, Station Biologique, B P 74, 29682 Roscoff Cedex, Bretagne, France
    Exp Cell Res 312:2394-400. 2006
    ..The relevance of this pharmacological synergism with respect to the treatment of neuroblastoma is discussed...
  38. ncbi request reprint Purification of CK1 by affinity chromatography on immobilised axin
    Jens Reinhardt
    Amyloids and Cell Division Cycle, Station Biologique de Roscoff, CNRS, Place Georges Teissier, 29680 Roscoff, France
    Protein Expr Purif 54:101-9. 2007
    ....
  39. ncbi request reprint Isolation of drugs active against mammalian prions using a yeast-based screening assay
    Stephane Bach
    C N R S, Station Biologique, Cell Cycle Laboratory, Place Georges Teissier, 29680 Roscoff, Bretagne, France
    Nat Biotechnol 21:1075-81. 2003
    ....
  40. ncbi request reprint Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum
    Marie Gompel
    C N R S, Cell Cycle Group, Station Biologique, B P 74, 29682 Roscoff Cedex, Bretagne, France
    Bioorg Med Chem Lett 14:1703-7. 2004
    ..These results suggest that meridianins constitute a promising scaffold from which more potent and selective protein kinase inhibitors could be designed...
  41. doi request reprint N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine
    Karima Bettayeb
    Centre National de la Recherche Scientifique, Protein Phosphorylation and Human Disease Group, UPS2682, Station Biologique, B P 74, 29682 Roscoff Cedex, Bretagne, France
    Mol Cancer Ther 7:2713-24. 2008
    ..Studies in mice show that N-&-N1 has pharmacokinetics properties similar to those of (R)-roscovitine. Altogether, these results show that analogues of (R)-roscovitine can be designed with improved antitumor potential...
  42. ncbi request reprint Pharmacological inhibitors of cyclin-dependent kinases
    Marie Knockaert
    Station Biologique de Roscoff, CNRS, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Trends Pharmacol Sci 23:417-25. 2002
    ..g. atherosclerosis and restenosis), glomerulonephritis, viral infections (e.g. HCMV, HIV and HSV) and parasitic protozoa (Plasmodium sp. and Leishmania sp.)...
  43. ncbi request reprint Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3
    Alexandra Testard
    Laboratoire de biotechnologies et de chimie bio organique, FRE CNRS 2766, UFR Sciences Fondamentales et Sciences pour l Ingénieur, Universite de La Rochelle, Batiment Marie Curie, 17042 La Rochelle, France
    Bioorg Med Chem Lett 16:3419-23. 2006
    ..Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme...
  44. ncbi request reprint A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors
    Lucie Vandromme
    UMR 176, Institut Curie, Bât 110 112, Centre Universitaire, 91405 Orsay, France
    Bioorg Med Chem 15:130-41. 2007
    ..Moderate in vitro inhibitory activity against CDK1 and CDK5 was observed with IC(50) of 0.9muM for the most active compound (18c)...
  45. ncbi request reprint Biosynthesis of new indigoid inhibitors of protein kinases using recombinant cytochrome P450 2A6
    Zhongliu Liu Wu
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 23rd and Pierce Avenues, Nashville, Tennessee 37232 0146, USA
    Chem Biodivers 2:51-65. 2005
    ..Thus, this system has the potential to generate new indigoids with therapeutic potential...
  46. ncbi request reprint Suzuki-type Pd(0) coupling reactions in the synthesis of 2-arylpurines as Cdk inhibitors
    Lucie Vandromme
    UMR 176 CNRS Institut Curie, Institut Curie Section de Recherche, Bat 110, Centre Universitaire, 91405 Orsay, France
    Bioorg Med Chem Lett 16:3144-6. 2006
    ..A new series of 2-aryl-substituted purine derivatives has been synthesized by Suzuki Pd(0) coupling reactions. Moderate in vitro inhibitory activity against Cdk1 and Cdk5 was observed. These compounds are inactive against GSK3...
  47. ncbi request reprint Synthesis of novel 5-substituted indirubins as protein kinases inhibitors
    Anne Beauchard
    Laboratoire de biotechnologies et de chimie bio organique, FRE CNRS 2766, UFR Sciences Fondamentales et Sciences pour l Ingénieur, Universite de La Rochelle, Batiment Marie Curie, 17042 La Rochelle, France
    Bioorg Med Chem 14:6434-43. 2006
    ..The effects of 34 indirubin derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3, as well as on SH-SY5Y human neuroblastoma cell survival, were investigated...
  48. ncbi request reprint An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted indirubins
    Vassilios Myrianthopoulos
    School of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771, Athens, Greece
    J Med Chem 50:4027-37. 2007
    ..Among these factors, the presence and treatment of structurally important water molecules had a pronounced impact on the quality of each model. The final model was validated by use of free energy perturbation calculations...
  49. doi request reprint Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex
    Aude Echalier
    Laboratory of Molecular Biophysics, Department of Biochemistry, The Rex Richards Building, University of Oxford, UK
    J Med Chem 51:737-51. 2008
    ....
  50. ncbi request reprint Structure-based design and synthesis of 2-benzylidene-benzofuran-3-ones as flavopiridol mimics
    Joseph Schoepfer
    Oncology Research, Novartis Pharma AG, 4002 Basle, Switzerland
    J Med Chem 45:1741-7. 2002
    ..Inhibitors of CDKs 1 and 2 that are more potent and selective than flavopiridol were obtained...
  51. doi request reprint Synthesis of 3,5-bis(2-indolyl)pyridine and 3-[(2-indolyl)-5-phenyl]pyridine derivatives as CDK inhibitors and cytotoxic agents
    Ulrich Jacquemard
    Institut de Chimie Organique et Analytique, 1 Université d Orléans, 2 CNRS UMR 6005, rue de Chartres, BP 6759, 45067 Orleans Cedex 2, France
    Bioorg Med Chem 16:4932-53. 2008
    ..Precise structure-activity relationships were delineated. Molecular modeling and docking solutions were proposed to complete the studies and to explain the observed SAR in the CDK assays...
  52. doi request reprint Photoreactivity of indirubin derivatives
    David Olivier
    HGRL, Laboratoire de Photobiologie des Cancers, Laser Department, 44093, Nantes, France
    Photochem Photobiol Sci 7:328-36. 2008
    ..These data could orientate further syntheses of either non-photoreactive compounds or compounds displaying both kinase inhibitory activity and strong phototoxicity...
  53. doi request reprint 9-cyano-1-azapaullone (cazpaullone), a glycogen synthase kinase-3 (GSK-3) inhibitor activating pancreatic beta cell protection and replication
    Hendrik Stukenbrock
    Institut fur Pharmazeutische Chemie, Technische Universitat Braunschweig, Beethovenstrasse 55, Braunschweig, Germany
    J Med Chem 51:2196-207. 2008
    ..These features distinguish cazpaullone as a unique starting point for the development of beta cell regenerative agents which might be useful in the treatment of diabetes...
  54. doi request reprint Butyrolactone I derivatives from Aspergillus terreus carrying an unusual sulfate moiety
    Xuemei Niu
    Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstrasse 11a, D 07745 Jena, Germany
    J Nat Prod 71:689-92. 2008
    ..Likewise, butyrolactone I 3-sulfate ( 1) exhibited moderate cytotoxicity solely against HeLa cells (CC 50 = 80.7 microM)...
  55. ncbi request reprint Epoxide-containing side chains enhance antiproliferative activity of paullones
    Xu Xie
    Institut fur Pharmazie, Universitat Hamburg, Bundesstrasse 45, D 20146 Hamburg, Germany
    Eur J Med Chem 40:655-61. 2005
    ....
  56. ncbi request reprint Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: synthesis, biological evaluation and molecular modeling studies
    Cedric Loge
    Universite de Nantes, Nantes Atlantique Universites, Biomolécules et Cibles Thérapeutiques, Departement de Pharmacochimie, BioCiT, UPRES EA 1155, UFR Sciences Pharmaceutiques, Nantes Cedex 1, France
    Eur J Med Chem 43:1469-77. 2008
    ..Combination of lead optimization and molecular modeling studies allowed identification of a dual CDK1/GSK-3 inhibitor (compound 13d) with submicromolar values...
  57. ncbi request reprint Synthesis of paullones with aminoalkyl side chains
    Karen Wieking
    Universitat Hamburg, Institut fur Pharmazie, Bundesstrasse 45, Germany
    Arch Pharm (Weinheim) 335:311-7. 2002
    ..Hence, 3 and 4 appear to be suitable tools for affinity studies directed to find additional intracellular paullone targets...
  58. ncbi request reprint Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activity evaluation of benzimidazole/benzoxazole derivatives and some Schiff's bases
    Sham M Sondhi
    Department of Chemistry, Indian Institute of Technology Roorkee IIT R, Roorkee 247 667, UA, India
    Bioorg Med Chem 14:3758-65. 2006
    ..6 microM) and CDK-1(IC(50)=7.4 microM) and compound 3a showed moderate CDK-5 inhibitory activity (IC(50)=7.5 microM). The other compounds showed moderate anti-inflammatory and analgesic activities...
  59. ncbi request reprint Synthesis and biological evaluation of novel phenylcarbazoles as potential anticancer agents
    Sylvain Routier
    Institut de Chimie Organique et Analytique, UMR CNRS 6005, Universite d Orleans, 45067 Orleans Cedex 2, France
    J Med Chem 49:789-99. 2006
    ..The efficient chemical routes reported here for the design of highly cytotoxic compounds provide novel opportunities to identify antitumor agents in the phenylcarbazole series...
  60. ncbi request reprint Synthesis and evaluation of the antiproliferative activity of novel thiazoloquinazolinone kinases inhibitors
    Alexandra Testard
    Laboratoire de Biotechnologies et Chimie Bio organique, FRE CNRS 2766, UFR Sciences Fondamentales et Sciences pour l Ingénieur, Batiment Marie Curie, Universite de La Rochelle, F l 7042 La Rochelle cedex 1, France
    J Enzyme Inhib Med Chem 20:557-68. 2005
    ..A lead compound was identified, constituting a scaffold from which more potent inhibitors could be designed...
  61. ncbi request reprint Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects
    Yvette Mettey
    Faculte de Medecine et de Pharmacie, 34 rue du Jardin des Plantes, B P 199, 86005 Poitiers Cedex, France
    J Med Chem 46:222-36. 2003
    ..Aloisine inhibits cell proliferation by arresting cells in both G1 and G2...
  62. ncbi request reprint CDK1-inhibitory activity of paullones depends on electronic properties of 9-substituents
    Tanja Pies
    Universitat Hamburg, Institut fur Pharmazie, Hamburg, Germany
    Arch Pharm (Weinheim) 337:486-92. 2004
    ..Among these new derivatives, 2-methoxy-9-methylsulfonylpaullone proved to be superior to the standard alsterpaullone with respect to CDK1 inhibition...
  63. pmc Inhibitors of Leishmania mexicana CRK3 cyclin-dependent kinase: chemical library screen and antileishmanial activity
    Karen M Grant
    Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom
    Antimicrob Agents Chemother 48:3033-42. 2004
    ..Thus, use of chemical inhibitors supports genetic studies to confirm CRK3 as a validated drug target in Leishmania and provides pharmacophores for further drug development...
  64. ncbi request reprint [Mediterranean purple indirubins: a source of GSK-3 inhibitors]
    Laurent Meijer
    Med Sci (Paris) 20:516-8. 2004
  65. ncbi request reprint Generation of new protein kinase inhibitors utilizing cytochrome p450 mutant enzymes for indigoid synthesis
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    J Med Chem 47:3236-41. 2004
    ..The general strategy may have additional applications...
  66. ncbi request reprint Synthesis and target identification of hymenialdisine analogs
    Yongqin Wan
    Genomics Institute of the Novartis Research Foundation, Department of Chemistry, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA
    Chem Biol 11:247-59. 2004
    ..The synthesis of HMD analogs has resulted in the identification of compounds with enhanced and/or dramatically altered selectivities relative to HMD (28n) and in molecules with antiproliferative activities 30-fold higher than HMD (28p)...
  67. ncbi request reprint 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta
    Conrad Kunick
    Institut fur Pharmazeutische Chemie, Technische Universitat Braunschweig, Beethovenstrasse 55, 38106, Braunschweig, Germany
    Bioorg Med Chem Lett 14:413-6. 2004
    ..The charge distribution within the 1-azakenpaullone molecule is discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1-azakenpaullone compared to other paullone derivatives...
  68. ncbi request reprint The inhibition of cyclin-dependent kinases induces differentiation of supernumerary hair cells and Deiters' cells in the developing organ of Corti
    Brigitte Malgrange
    Center for Cellular and Molecular Neurobiology, University of Liege, 17 Place Delcour, B 4020 Liege, Belgium
    FASEB J 17:2136-8. 2003
    ....
  69. ncbi request reprint Cyclin-dependent kinase inhibitors
    Peter M Fischer
    Cyclacel Limited, Dundee, DD1 5JJ, Scotland, U K
    Prog Cell Cycle Res 5:235-48. 2003
    ..The requirement for CDKs in many physiological processes justifies their evaluation as potential therapeutic targets against a much larger scope of diseases than initially anticipated...
  70. ncbi request reprint Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases
    Panagiotis Polychronopoulos
    Laboratory of Pharmacognosy and Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771 Athens, Greece
    J Med Chem 47:935-46. 2004
    ..Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1...
  71. ncbi request reprint Synthesis and biological evaluation of thienopyrrolizines, a new family of CDK/GSK-3 inhibitors
    Christophe Rochais
    Centre d Etudes et de Recherche sur le Medicament de Normandie, Universite de Caen Basse Normandie, 14032 Caen Cedex, France
    J Enzyme Inhib Med Chem 19:585-93. 2004
    ..Its molecular modeling study brought to the fore the pivotal role of the 2-methoxyphenol grouping and the interest in replacing it by bioisosteric moieties in future pharmacomodulations...
  72. ncbi request reprint Novel CDK inhibition profiles of structurally varied 1-aza-9-oxafluorenes
    Burkhardt Voigt
    Institute of Pharmaceutical Chemistry, Department of Pharmacy, Martin Luther University Halle Wittenberg, Wolfgang Langenbeck Str 4, 06120 Halle, Germany
    Bioorg Med Chem Lett 15:823-5. 2005
    ..The absence of a 3-hydrogen bond acceptor function leads to a complete loss of inhibitory activity. Differing hydrogen bond acceptor functions surprisingly cause significant shifts in the selectivity of inhibition profiles...
  73. ncbi request reprint Evaluation and comparison of 3D-QSAR CoMSIA models for CDK1, CDK5, and GSK-3 inhibition by paullones
    Conrad Kunick
    Institut fur Pharmazie, Abteilung für Pharmazeutische Chemie, Universitat Hamburg, Bundesstrasse 45, D 20146 Hamburg, Germany
    J Med Chem 47:22-36. 2004
    ..929 and q(2)() = 0.699), which were clearly superior to the models for CDK5 (r(2)() = 0.874 and q(2)() = 0.652) and GSK-3 (r(2)() = 0.871 and q(2)() = 0.554)...
  74. ncbi request reprint Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives
    Lin Tang
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China
    J Biol Chem 280:31220-9. 2005
    ..This work provides detailed structural information on the interactions between PDXK and roscovitine and analogs. It could also aid in the design of roscovitine derivatives displaying strict selectivity for either PDXK or CDKs...
  75. ncbi request reprint Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities
    Sham M Sondhi
    Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India
    Bioorg Med Chem 13:4291-9. 2005
    ..o. A compound, 4o (R1 = H, R2 = OCH3, R3 = CH3, R4 = CH3, R5 = H) exhibited moderate CDK1 (IC50 = 8.5 microM) inhibition activity...
  76. pmc Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity
    Jacek Biernat
    Max Planck Unit for Structural Molecular Biology, Hamburg, Germany
    Mol Biol Cell 13:4013-28. 2002
    ..The results suggest that MARK2 contributes to the plasticity of microtubules needed for neuronal polarity and the growth of neurites...
  77. ncbi request reprint Structure-aided optimization of kinase inhibitors derived from alsterpaullone
    Conrad Kunick
    Institut fur Pharmazeutische Chemie, Technische Universitat Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany
    Chembiochem 6:541-9. 2005
    ..The novel 2-cyanoethylalsterpaullone (7) proved to be the most potent paullone described so far, exhibiting inhibitory concentrations for CDK1/ cyclin B and GSK-3beta in the picomolar range...
  78. ncbi request reprint Pyrazolo[3,4-c]pyridazines as novel and selective inhibitors of cyclin-dependent kinases
    Miguel F Braña
    Facultad de Farmacia, Universidad San Pablo CEU, Urbanizacion Monteprincipe, 28668 Boadilla del Monte, Madrid, Spain
    J Med Chem 48:6843-54. 2005
    ..As a result of the SAR study, monofuryl 1o has been synthesized and is one of the most active compounds against CDK1 of this series...
  79. ncbi request reprint Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin
    Heshu Lu
    Physical Biosciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 64R0121, Berkeley, California 94720, USA
    J Med Chem 48:737-43. 2005
    ..This complex structure is the first description of an inhibitor complex with a kinase from the CDK4/6 subfamily and can provide a basis for selecting and designing inhibitor compounds with higher affinities and specificities...
  80. ncbi request reprint Protein kinases as drug targets in parasitic protozoa
    Christian Doerig
    Institut National de la Sante et de la Recherche Medicale, U 511, CHU Pitie Salpetriere, 91 Bd de l Hopital, 75013 Paris, France
    Trends Parasitol 18:366-71. 2002
    ..In addition, screening chemical libraries with active recombinant protein kinases can identify lead compounds for drug design...
  81. ncbi request reprint Synthesis of 3-substituted-2-oxoindole analogues and their evaluation as kinase inhibitors, anticancer and antiangiogenic agents
    Ashraf H Abadi
    Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Egypt
    Eur J Med Chem 41:296-305. 2006
    ..Thus, the antiangiogenesis properties are not apparently caused by inhibition of any of the tested kinases...
  82. doi request reprint Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1
    Nassima Oumata
    Laboratoire de Chimie Organique 2, INSERM U 648, Universite Paris Descartes, 4 avenue de l Observatoire, 75270 Paris Cedex 06, France
    J Med Chem 51:5229-42. 2008
    ..13a was able to prevent the CK1-dependent production of amyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers...
  83. ncbi request reprint Cyclin-dependent kinase inhibitor indirubin-3'-oxime selectively inhibits human papillomavirus type 16 E7-induced numerical centrosome anomalies
    Stefan Duensing
    Molecular Virology Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
    Oncogene 23:8206-15. 2004
    ..Our results suggest that cyclin/CDK2 activity is critically involved in abnormal centrosome duplication induced by HPV-16 E7 oncoprotein expression, but may be dispensable for normal centrosome duplication and cell cycle progression...
  84. ncbi request reprint Characterization of two T. gondii CK1 isoforms
    Robert G K Donald
    Department of Human Animal Infectious Disease Research, Merck Research Laboratories, Merck and Co, P O Box 2000, R80Y 260, Rahway, NJ 07065 0900, USA
    Mol Biochem Parasitol 141:15-27. 2005
    ..Since the more cell-permeable aminopurvalanol also inhibits parasite growth, these results provide further impetus to investigate inhibitors of CK1 as anti-parasitic agents...
  85. pmc Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus type 1 by targeting cellular, not viral, proteins
    Luis M Schang
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Virol 76:7874-82. 2002
    ..Lastly, the spectrum of proteins that bound to P-PCIs in extracts of mock- and HSV-infected cells was the same. Based on these observations, we conclude that P-PCIs inhibit virus replication by targeting cellular, not viral, proteins...
  86. ncbi request reprint Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties
    Kristin Brachwitz
    Institute of Pharmaceutical Chemistry, Martin Luther University Halle Wittenberg, Wolfgang Langenbeck Strasse 4, 06120 Halle, Germany
    J Med Chem 46:876-9. 2003
    ..Compounds were shown to inhibit the membrane-efflux pump P-glycoprotein responsible for multidrug resistance in cancer cells. First structure-activity relationships are discussed...
  87. ncbi request reprint Mechanism of CDK5/p25 binding by CDK inhibitors
    Marina Mapelli
    Structural Biology Unit, Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    J Med Chem 48:671-9. 2005
    ..The CDK5/p25 crystals represent a valuable new tool for the identification and optimization of selective CDK inhibitors...