Pascal Furet

Summary

Affiliation: Novartis Institutes for BioMedical Research

Publications

  1. doi request reprint Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805
    Fabienne Baffert
    Disease Area Oncology, Novartis Institutes for BioMedical Research, 4057 Basel, Switzerland
    Mol Cancer Ther 9:1945-55. 2010
  2. doi request reprint The central valine concept provides an entry in a new class of non peptide inhibitors of the p53-MDM2 interaction
    Pascal Furet
    Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 22:3498-502. 2012
  3. doi request reprint Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 26:4837-41. 2016
  4. doi request reprint Entry into a new class of protein kinase inhibitors by pseudo ring design
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 18:897-900. 2008
  5. ncbi request reprint Aromatic interactions with phenylalanine 691 and cysteine 828: a concept for FMS-like tyrosine kinase-3 inhibition. Application to the discovery of a new class of potential antileukemia agents
    Pascal Furet
    Novartis Pharma AG, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    J Med Chem 49:4451-4. 2006
  6. doi request reprint Design of two new chemotypes for inhibiting the Janus kinase 2 by scaffold morphing
    Pascal Furet
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    Bioorg Med Chem Lett 20:1858-60. 2010
  7. doi request reprint Discovery of a new class of catalytic topoisomerase II inhibitors targeting the ATP-binding site by structure based design. Part I
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 19:4014-7. 2009
  8. doi request reprint Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
    Sauveur Michel Maira
    Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
    Mol Cancer Ther 7:1851-63. 2008
  9. ncbi request reprint Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design
    Pascal Furet
    Novartis Pharma AG, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    J Med Chem 47:4810-3. 2004
  10. ncbi request reprint Urea derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases
    Paul W Manley
    Disease Area Oncology, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 14:5793-7. 2004

Detail Information

Publications58

  1. doi request reprint Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805
    Fabienne Baffert
    Disease Area Oncology, Novartis Institutes for BioMedical Research, 4057 Basel, Switzerland
    Mol Cancer Ther 9:1945-55. 2010
    ..Furthermore, NVP-BSK805 potently suppressed recombinant human erythropoietin-induced polycythemia and extramedullary erythropoiesis in mice and rats...
  2. doi request reprint The central valine concept provides an entry in a new class of non peptide inhibitors of the p53-MDM2 interaction
    Pascal Furet
    Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 22:3498-502. 2012
    ..The design of molecules based on this concept has allowed us to rapidly identify compounds having a 3-imidazolyl indole core structure as the first representatives of a new class of potent inhibitors of the p53-MDM2 interaction...
  3. doi request reprint Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 26:4837-41. 2016
    ..This work forms the foundation of the discovery of HDM201, a second generation p53-MDM2 inhibitor that recently entered phase I clinical trial. ..
  4. doi request reprint Entry into a new class of protein kinase inhibitors by pseudo ring design
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 18:897-900. 2008
    ..Potent inhibition of a number of protein kinases was obtained with the first prototype compound synthesized to probe the design concept...
  5. ncbi request reprint Aromatic interactions with phenylalanine 691 and cysteine 828: a concept for FMS-like tyrosine kinase-3 inhibition. Application to the discovery of a new class of potential antileukemia agents
    Pascal Furet
    Novartis Pharma AG, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    J Med Chem 49:4451-4. 2006
    ..The hypothesis has been validated by the successful design of a new inhibitor prototype showing promising antiproliferative activity in cellular assays...
  6. doi request reprint Design of two new chemotypes for inhibiting the Janus kinase 2 by scaffold morphing
    Pascal Furet
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    Bioorg Med Chem Lett 20:1858-60. 2010
    ..Starting from a screening hit, two new JAK2 inhibitor chemotypes were designed by scaffold morphing. The prototype compounds of these new series showed nanomolar inhibition of the kinase...
  7. doi request reprint Discovery of a new class of catalytic topoisomerase II inhibitors targeting the ATP-binding site by structure based design. Part I
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 19:4014-7. 2009
    ..Searching the Novartis compound collection for molecules containing this purine motif has allowed the identification of two micromolar hits providing access to a new class of catalytic topoisomerase II inhibitors...
  8. doi request reprint Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
    Sauveur Michel Maira
    Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
    Mol Cancer Ther 7:1851-63. 2008
    ..Collectively, the preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties. NVP-BEZ235 is currently in phase I clinical trials...
  9. ncbi request reprint Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design
    Pascal Furet
    Novartis Pharma AG, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    J Med Chem 47:4810-3. 2004
    ..We report here the design, synthesis, and biological characterization of prototypes of a new class of noncovalent proteasome inhibitors showing high activity in biochemical and cellular assays...
  10. ncbi request reprint Urea derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases
    Paul W Manley
    Disease Area Oncology, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 14:5793-7. 2004
    ..It was also possible to differentiate between c-Abl and PDGFR kinase inhibition, with compound 22 being selective towards Abl and 23 selective for PDGFR...
  11. doi request reprint Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site
    Doriano Fabbro
    Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland
    Biochim Biophys Acta 1804:454-62. 2010
    ....
  12. doi request reprint Binding or bending: distinction of allosteric Abl kinase agonists from antagonists by an NMR-based conformational assay
    Wolfgang Jahnke
    Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland
    J Am Chem Soc 132:7043-8. 2010
    ..Activation of c-Abl by allosteric agonists has been confirmed in a biochemical assay...
  13. ncbi request reprint Novel beta-lactam derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome
    Patricia Imbach
    Novartis Institutes for BioMedical Research, WKL 136 4 25, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 17:358-62. 2007
    ....
  14. pmc Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia
    Sandra W Cowan-Jacob
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    Acta Crystallogr D Biol Crystallogr 63:80-93. 2007
    ..These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery...
  15. ncbi request reprint Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment
    Sandra W Cowan-Jacob
    Novartis Institutes of Biomedical Research, CH 4057, Basel, Switzerland
    Mini Rev Med Chem 4:285-99. 2004
    ..Strategies to potentially circumvent or overcome resistance are discussed...
  16. doi request reprint Discovery and SAR of potent, orally available 2,8-diaryl-quinoxalines as a new class of JAK2 inhibitors
    Carole Pissot-Soldermann
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, WKL 136 4 96, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 20:2609-13. 2010
    ..In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation...
  17. pmc Crystal Structures of Human MdmX (HdmX) in Complex with p53 Peptide Analogues Reveal Surprising Conformational Changes
    Joerg Kallen
    Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    J Biol Chem 284:8812-21. 2009
    ..They also reveal possible conformational states of HdmX, which should lead to a better prediction of its interactions with potential biological partners...
  18. doi request reprint Extended kinase profile and properties of the protein kinase inhibitor nilotinib
    Paul W Manley
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    Biochim Biophys Acta 1804:445-53. 2010
    ..Although neither enzymatic nor cellular data are yet available to substantiate the drug as an inhibitor of ZAK phosphorylation, modeling predicts that it binds in an ATP-competitive fashion...
  19. ncbi request reprint Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis
    Paul William Manley
    Novartis Institutes of Biomedical Research, WKL 136 4 86, CH 4002 Basel, Switzerland
    Biochim Biophys Acta 1697:17-27. 2004
    ..This binding mode, similar to that observed for the anti-leukemia drug, imatinib in complex with c-Abl kinase, may be responsible for the high selectivity of AAL993 and provides valuable insight for the design of further compounds...
  20. doi request reprint 2-Amino-aryl-7-aryl-benzoxazoles as potent, selective and orally available JAK2 inhibitors
    Marc Gerspacher
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 20:1724-7. 2010
    ..Synthesis and structure-activity relationship data are also provided...
  21. doi request reprint Identification and optimisation of 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole and 4,5-dihydrothiazolo[4,5-h]quinazoline series of selective phosphatidylinositol-3 kinase alpha inhibitors
    Robin A Fairhurst
    Novartis Institutes for BioMedical Research, Global Discovery Chemistry, Novartis Pharma AG, Werk Klybeck, Postfach, CH 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 25:3575-81. 2015
    ..From this work analogues including 11, 12, 19 and 23 were identified as potent and selective PI3Kα inhibitor in vivo tool compounds. ..
  22. ncbi request reprint Discovery of a potent and selective protein kinase CK2 inhibitor by high-throughput docking
    Eric Vangrevelinghe
    Oncology Research, Novartis Pharma AG, 4002 Basle, Switzerland
    J Med Chem 46:2656-62. 2003
    ..The results obtained suggest that virtual screening of a 3D database by molecular docking is a useful approach for lead finding provided that adapted postdocking filtering and reranking procedures are applied to the primary hit list...
  23. doi request reprint A drug resistance screen using a selective MET inhibitor reveals a spectrum of mutations that partially overlap with activating mutations found in cancer patients
    Ralph Tiedt
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    Cancer Res 71:5255-64. 2011
    ..Compounds binding in the same manner as NVP-BVU972 might be particularly susceptible to the development of resistance through mutations in Y1230, a condition that may be addressed by MET inhibitors with alternative binding modes...
  24. pmc The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis
    Georg Martiny-Baron
    Novartis Institutes for BioMedical Research, Expertise Platform Kinases, Novartis Campus, Fabrikstrasse 16, WJS152 1 72 2, 4056 Basel, Switzerland
    Angiogenesis 13:259-67. 2010
    ....
  25. ncbi request reprint X-ray crystallographic studies of CDK2, a basis for cyclin-dependent kinase inhibitor design in anti-cancer drug research
    Pascal Furet
    Novartis Pharma Inc, Oncology Research Department, CH 4002 Basel, Switzerland
    Curr Med Chem Anticancer Agents 3:15-23. 2003
    ..The use of this information to design or optimize CDK inhibitors by molecular modeling is also reviewed...
  26. doi request reprint Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction
    Andrea Vaupel
    Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 24:2110-4. 2014
    ..An appropriate strategy has allowed us to translate the high biochemical potency in significant anti-proliferative activity on a p53-dependent MDM2 amplified cell line...
  27. doi request reprint Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53-MDM2 interaction with a distinct binding mode
    Francois Gessier
    Novartis Institutes for BioMedical Research, WKL 136 P 12, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 25:3621-5. 2015
    ..The X-ray structure revealed an unprecedented binding mode for p53-MDM2 inhibitors. ..
  28. doi request reprint Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation
    Pascal Furet
    Novartis Institutes for BioMedical Research, WKL 136 4 12, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 23:3741-8. 2013
    ....
  29. doi request reprint Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase
    Vito Guagnano
    Novartis Institute for Biomedical Research, CH 4002 Basel, Switzerland
    J Med Chem 54:7066-83. 2011
    ..These results support the potential therapeutic use of 1h as a new anticancer agent...
  30. ncbi request reprint Identification of a new chemical class of potent angiogenesis inhibitors based on conformational considerations and database searching
    Pascal Furet
    Oncology Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 13:2967-71. 2003
    ..This could be achieved with a limited experimental effort, which only involved the testing of one archive compound and the synthesis and testing of one appropriate analogue...
  31. doi request reprint Identification and optimisation of a 4',5-bisthiazole series of selective phosphatidylinositol-3 kinase alpha inhibitors
    Robin A Fairhurst
    Novartis Institutes for BioMedical Research, Global Discovery Chemistry, Novartis Pharma AG, Werk Klybeck, Postfach, CH 4002 Basel, Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 25:3569-74. 2015
    ..From this work a number of analogues, including 14 (A66) and 24, were identified as potent and selective PI3Kα inhibitor in vitro tool compounds. ..
  32. ncbi request reprint Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors
    Paul W Manley
    Oncology Research, Novartis Pharma AG, Basel, Switzerland
    J Med Chem 45:5687-93. 2002
    ..The anthranilamides 5 and 7 represent a new structural class of VEGFR kinase inhibitors, which possess potent antiangiogenic and antitumor properties...
  33. ncbi request reprint In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase
    Carlos Garcia-Echeverria
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Cancer Cell 5:231-9. 2004
    ..Thus, NVP-AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application...
  34. doi request reprint New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck
    Nina Gommermann
    Novartis Institute of Biomedical Research, Forum 1, Novartis Campus, Basel, Switzerland
    Bioorg Med Chem Lett 20:3628-31. 2010
    ..An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymatic, cellular and in vivo potency...
  35. doi request reprint A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis
    Guido Bold
    Oncology Research, Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland
    J Med Chem 59:132-46. 2016
    ..This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role. ..
  36. doi request reprint Knowledge-based virtual screening: application to the MDM4/p53 protein-protein interaction
    Edgar Jacoby
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
    Methods Mol Biol 575:173-94. 2009
    ..Novel, selective and dual hits are discovered for both systems. A hit rate analysis will be provided compared to the full HTS (High-throughput Screening)...
  37. doi request reprint New aromatase inhibitors from the 3-pyridyl arylether and 1-aryl pyrrolo[2,3-c]pyridine series
    Frederic Stauffer
    Novartis Institutes for BioMedical Research, Global Discovery Chemistry Oncology, Postfach, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 22:1860-3. 2012
    ..Potent and ligand efficient leads such as compound 23 (IC(50)=59nM on aromatase) have been identified...
  38. doi request reprint Discovery of novel anticancer therapeutics targeting the PI3K/Akt/mTOR pathway
    Sauveur Michel Maira
    NIBR GDC and Oncology, Novartis Pharma AG, CH4002 Basel, Switzerland
    Future Med Chem 1:137-55. 2009
    ..The large amount of published clinical and preclinical data has indeed confirmed the preponderant role of this so-called survival pathway for tumor maintenance...
  39. doi request reprint Discovery of a novel tricyclic 4H-thiazolo[5',4':4,5]pyrano[2,3-c]pyridine-2-amino scaffold and its application in a PI3Kα inhibitor with high PI3K isoform selectivity and potent cellular activity
    Marc Gerspacher
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, WKL 136 4 84, CH 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 25:3582-4. 2015
    ..The application of this novel chemotype leading to a potent and selective prototype PI3Kα inhibitor with favorable physicochemical and PK-properties is described. ..
  40. ncbi request reprint Protein kinases as targets for anticancer agents: from inhibitors to useful drugs
    Doriano Fabbro
    Department of Oncology, Novartis Pharma Inc, WKL 125 4 10, CH 4002, Basel, Switzerland
    Pharmacol Ther 93:79-98. 2002
    ..Phase I/II studies demonstrated that STI571 is well tolerated, and that it showed promising hematological and cytogenetic responses in CML and clinical responses in the c-Kit-driven gastrointestinal tumors...
  41. doi request reprint Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors
    Philipp Holzer
    Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland
    J Med Chem 58:6348-58. 2015
    ..The following aspects are addressed: mechanism of action, scientific rationale, binding mode, medicinal chemistry, pharmacokinetic and pharmacodynamic properties, and in vivo pharmacology/toxicology in preclinical species. ..
  42. doi request reprint The TEAD4-YAP/TAZ protein-protein interaction: expected similarities and unexpected differences
    Jean Christophe Hau
    Disease Area Oncology, Novartis Institutes for BioMedical Research, 141 Klybeckstrasse, 4057 Basel, Switzerland
    Chembiochem 14:1218-25. 2013
    ..This convergent optimization of the YAP/TAZ TEAD binding site suggests that the similarity in the affinities of binding of YAP to TEAD and of TAZ to TEAD is important for Hippo pathway functionality. ..
  43. 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...
  44. ncbi request reprint Structure-based optimisation of 2-aminobenzylstatine derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome
    Pascal Furet
    Oncology Research, Novartis Pharma Inc, CH 4002, Basel, Switzerland
    Bioorg Med Chem Lett 12:1331-4. 2002
    ..The new derivatives showed good selectivity against the trypsin-like and post-glutamyl-peptide hydrolytic activities of this enzyme...
  45. doi request reprint Optimisation of a 5-[3-phenyl-(2-cyclic-ether)-methyl-ether]-4-aminopyrrolopyrimidine series of IGF-1R inhibitors
    Robin A Fairhurst
    Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 26:2057-64. 2016
    ..Compound 33 showed improved selectivity and pharmacokinetics compared to NVP-AEW541, and produced comparable in vivo efficacy to linsitinib in inhibiting the growth of an IGF-1R dependent tumour xenograft model in the mouse. ..
  46. pmc A distinct p53 target gene set predicts for response to the selective p53-HDM2 inhibitor NVP-CGM097
    Sébastien Jeay
    Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland
    elife 4:. 2015
    ....
  47. doi request reprint Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway
    Frederic Stauffer
    Novartis Institute for Biomedical Research, Oncology Drug Discovery, Klybeckstrasse 141, Postfach, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 18:1027-30. 2008
    ..The SAR data of representative examples of this compound class and their biological profiling in cellular and in vivo settings are presented and discussed...
  48. ncbi request reprint Study of the cytotoxic effect of a peptidic inhibitor of the p53-hdm2 interaction in tumor cells
    Patrick Chene
    Oncology Department, Novartis K125 442, CH 4002 Basel, Switzerland
    FEBS Lett 529:293-7. 2002
    ..The peptide is also less toxic for non-tumor cells than for tumor cells overexpressing the hdm2 protein...
  49. pmc Catalytic inhibition of topoisomerase II by a novel rationally designed ATP-competitive purine analogue
    Patrick Chene
    Department of Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland
    BMC Chem Biol 9:1. 2009
    ..Thus, interfering with ATPase function with low molecular weight inhibitors that target the nucleotide binding pocket should profoundly affect cells that are committed to undergo mitosis...
  50. ncbi request reprint Structure-based design and protein X-ray analysis of a protein kinase inhibitor
    Pascal Furet
    Novartis Pharmaceuticals Inc, Oncology Research, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 12:221-4. 2002
    ..In addition, it revealed an alternative binding orientation involving a second tautomeric form of the inhibitor that was not envisaged during the design stage...
  51. doi request reprint Identification of a 5-[3-phenyl-(2-cyclic-ether)-methylether]-4-aminopyrrolo[2,3-d]pyrimidine series of IGF-1R inhibitors
    Frederic Stauffer
    Novartis Institutes for BioMedical Research, Basel, Postfach, 4002 Basel, Switzerland Electronic address
    Bioorg Med Chem Lett 26:2065-7. 2016
    ..We show that 1,4-diethers displaying an adequate hydrophobic and constrained shape are advantageous benzyloxy replacements. A single digit nanomolar inhibitor (compound 20, IC50=8.9 nM) was identified following this approach...
  52. ncbi request reprint Total synthesis and biological evaluation of a C(10)/C(12)-phenylene-bridged analog of epothilone D
    Nicole End
    Novartis Institutes for BioMedical Research, DA Oncology, CH 4002 Basel
    Chem Biodivers 1:1771-84. 2004
    ..Although 8 had been suggested by pharmacophore modeling to adopt a conformation similar to the bioactive conformation of epothilone B, the compound was devoid of any significant antiproliferative activity...
  53. pmc Discovery and Pharmacological Characterization of Novel Quinazoline-Based PI3K Delta-Selective Inhibitors
    Klemens Hoegenauer
    Global Discovery Chemistry, Center for Proteomic Chemistry, Metabolism and Pharmacokinetics, Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Novartis Campus, CH 4002 Basel, Switzerland
    ACS Med Chem Lett 7:762-7. 2016
    ..After oral administration of compound 11 to rats, proximal PD markers are inhibited, and dose-dependent efficacy in a mechanistic plaque forming cell assay could be demonstrated. ..
  54. doi request reprint Bioorthogonal Probes for the Study of MDM2-p53 Inhibitors in Cells and Development of High-Content Screening Assays for Drug Discovery
    Pier Luca D'Alessandro
    Global Discovery Chemistry, Novartis Institutes of Biomedical Research, Novartis Campus, Basel, Switzerland
    Angew Chem Int Ed Engl . 2016
    ..This approach could be expanded to other targets for lead discovery applications...
  55. pmc Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA)
    Stefania Sarno
    Venetian Institute for Molecular Medicine VIMM, University of Padova, 35121 Padova, Italy
    Biochem J 374:639-46. 2003
    ..These results provide new tools for deciphering the enigmatic role of CK2 in living cells and may pave the way for the development of drugs depending on CK2 activity...
  56. ncbi request reprint Salicylanilides as inhibitors of the protein tyrosine kinase epidermal growth factor receptor
    Christoph Liechti
    Department of Chemistry, University of Basel, St Johanns Ring 19, CH 4056 Basel, Switzerland
    Eur J Med Chem 39:11-26. 2004
    ..Some of them indeed proved to be potent and selective EGFR tyrosine kinase inhibitors. The most potent ones being 28, 16, 20, 6, and 15, with IC(50) in the 23-71 nM range...
  57. ncbi request reprint Prediction of resistance to small molecule FLT3 inhibitors: implications for molecularly targeted therapy of acute leukemia
    Jan Cools
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Cancer Res 64:6385-9. 2004
    ....
  58. ncbi request reprint Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy
    Ariane Jansma
    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA
    J Med Chem 50:5875-7. 2007
    ..A scalar coupling across the hydrogen bond was detected in organic and aqueous solvent, suggesting a simple and general approach for testing the propensity of intramolecular hydrogen bonds to stabilize pseudo-rings in drug scaffolds...