Signal transduction therapy with rationally designed kinase inhibitors

[1]  N. Keen,et al.  Progress in the development of selective inhibitors of aurora kinases. , 2005, Current topics in medicinal chemistry.

[2]  J. Melo,et al.  The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. , 1997, Blood.

[3]  L. Tong,et al.  Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site , 2002, Nature Structural Biology.

[4]  K. Kolibaba,et al.  Protein tyrosine kinases and cancer. , 1997, Biochimica et biophysica acta.

[5]  H. Mori,et al.  Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. , 1999, Cancer research.

[6]  R. Cramer,et al.  Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. , 1988, Journal of the American Chemical Society.

[7]  Keisuke Kuida,et al.  Inhibitors of Protein Kinase Signaling Pathways: Emerging Therapies for Cardiovascular Disease , 2004, Circulation.

[8]  Chemical genomics versus orthodox drug development. , 2003, Drug discovery today.

[9]  J. Bartek,et al.  Inhibition of Human Chk1 Causes Increased Initiation of DNA Replication, Phosphorylation of ATR Targets, and DNA Breakage , 2005, Molecular and Cellular Biology.

[10]  Ola Engkvist,et al.  Characterization of a conserved structural determinant controlling protein kinase sensitivity to selective inhibitors. , 2004, Chemistry & biology.

[11]  J Mottram,et al.  Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. , 2000, Chemistry & biology.

[12]  M. Cotten,et al.  An efficient proteomics method to identify the cellular targets of protein kinase inhibitors , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  H. Jhoti,et al.  The Discovery of Novel Protein Kinase Inhibitors by Using Fragment‐Based High‐Throughput X‐ray Crystallography , 2005, Chembiochem : a European journal of chemical biology.

[14]  G. Klebe,et al.  Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. , 1994, Journal of medicinal chemistry.

[15]  A. Bridges The rationale and strategy used to develop a series of highly potent, irreversible, inhibitors of the epidermal growth factor receptor family of tyrosine kinases. , 1999, Current medicinal chemistry.

[16]  P. Seeburg,et al.  Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells , 1984, Nature.

[17]  M. Champe,et al.  Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states. , 1999, Journal of molecular biology.

[18]  R. K Srivastava,et al.  Pro-survival Function of Akt/Protein Kinase B in Prostate Cancer Cells , 2001, The Journal of Biological Chemistry.

[19]  A. Levitzki,et al.  Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors. , 1989, Journal of medicinal chemistry.

[20]  Hugo Kubinyi,et al.  Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective , 2004 .

[21]  J. Mestan,et al.  Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis. , 2004, Biochimica et biophysica acta.

[22]  Paul S. Charifson,et al.  Practical Application of Computer-Aided Drug Design , 1997 .

[23]  H. Fine,et al.  Results from phase II trial of enzastaurin (LY317615) in patients with recurrent high grade gliomas , 2005 .

[24]  A. Doherty,et al.  In vitro pharmacological characterization of PD 166285, a new nanomolar potent and broadly active protein tyrosine kinase inhibitor. , 1997, The Journal of pharmacology and experimental therapeutics.

[25]  Sebastian Meier-Ewert,et al.  A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. , 2004, Chemistry & biology.

[26]  J. Christensen,et al.  c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. , 2005, Cancer letters.

[27]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[28]  P. Changelian,et al.  The Novel JAK‐3 Inhibitor CP‐690550 Is a Potent Immunosuppressive Agent in Various Murine Models , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[29]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings , 1997 .

[30]  A. Hopkins,et al.  The druggable genome , 2002, Nature Reviews Drug Discovery.

[31]  M. Sliwkowski,et al.  Structure of the Epidermal Growth Factor Receptor Kinase Domain Alone and in Complex with a 4-Anilinoquinazoline Inhibitor* , 2002, The Journal of Biological Chemistry.

[32]  E. Sausville,et al.  Issues and progress with protein kinase inhibitors for cancer treatment , 2003, Nature Reviews Drug Discovery.

[33]  P. Cohen,et al.  The regulation of protein function by multisite phosphorylation--a 25 year update. , 2000, Trends in biochemical sciences.

[34]  M. Müller,et al.  A new method for a quantitative assessment of P-glycoprotein-related multidrug resistance in tumour cells. , 1996, British Journal of Cancer.

[35]  G. Kéri,et al.  New antitumor leads from a peptidomimetic library , 1999, Letters in Peptide Science.

[36]  L. Wodicka,et al.  A small molecule–kinase interaction map for clinical kinase inhibitors , 2005, Nature Biotechnology.

[37]  J. Siekierka,et al.  6-Amino-2-(4-fluorophenyl)-4-methoxy-3- (4-pyridyl)-1H-pyrrolo[2, 3-b]pyridine (RWJ 68354): a potent and selective p38 kinase inhibitor. , 1998, Journal of medicinal chemistry.

[38]  J. Boehm,et al.  Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity. , 2001, Bioorganic & medicinal chemistry letters.

[39]  Krystal J Alligood,et al.  A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib) , 2004, Cancer Research.

[40]  L. Meijer,et al.  Intracellular Targets of Paullones , 2002, The Journal of Biological Chemistry.

[41]  L. Kuyper,et al.  Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. , 2000, Journal of medicinal chemistry.

[42]  H. Burris,et al.  Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib. , 2004, The oncologist.

[43]  F. Rastinejad,et al.  Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy. , 2003, Cancer research.

[44]  D. Troyer,et al.  Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[45]  J. Warmus,et al.  Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition , 2004, Nature Structural &Molecular Biology.

[46]  O. Hensens,et al.  Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK. , 1999, The Journal of antibiotics.

[47]  N. Ferrara Role of vascular endothelial growth factor in regulation of physiological angiogenesis. , 2001, American journal of physiology. Cell physiology.

[48]  K. Caca,et al.  Molecularly targeted therapy for gastrointestinal cancer. , 2005, Current cancer drug targets.

[49]  K. Fukasawa,et al.  Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. , 2001, Journal of medicinal chemistry.

[50]  S. Hubbard,et al.  Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain , 1998, The EMBO journal.

[51]  Jing-Yuan Fang,et al.  The MAPK signalling pathways and colorectal cancer. , 2005, The Lancet. Oncology.

[52]  James R. Burke,et al.  BMS-345541 Is a Highly Selective Inhibitor of IκB Kinase That Binds at an Allosteric Site of the Enzyme and Blocks NF-κB-dependent Transcription in Mice* , 2003, The Journal of Biological Chemistry.

[53]  P. Furet,et al.  Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. , 1999, Pharmacology & therapeutics.

[54]  J. Mestan,et al.  AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. , 2004, Cancer research.

[55]  J. Cherrington,et al.  Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents , 2003, Expert opinion on investigational drugs.

[56]  K. Gumireddy,et al.  A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistance. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[57]  G. Kéri,et al.  Molecular Pathomechanisms and New Trends in Drug Research , 2007 .

[58]  C. Dominguez,et al.  p38 MAP kinase inhibitors: many are made, but few are chosen. , 2005, Current opinion in drug discovery & development.

[59]  György Kéri,et al.  Cellular targets of gefitinib. , 2005, Cancer research.

[60]  Peter Zbinden,et al.  Quasi-Atomistic Receptor Surface Models: A Bridge between 3-D QSAR and Receptor Modeling , 1998 .

[61]  L. Meijer,et al.  Synthesis and target identification of hymenialdisine analogs. , 2004, Chemistry & biology.

[62]  N. Pavletich Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. , 1999, Journal of molecular biology.

[63]  W. Jiang,et al.  Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. , 2005, Critical reviews in oncology/hematology.

[64]  M. Maccoss,et al.  Pyrroles and other heterocycles as inhibitors of p38 kinase. , 1998, Bioorganic & medicinal chemistry letters.

[65]  Á. Furka,et al.  General method for rapid synthesis of multicomponent peptide mixtures. , 2009, International journal of peptide and protein research.

[66]  J. Boehm,et al.  p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases , 2003, Nature Reviews Drug Discovery.

[67]  S. Hubbard,et al.  Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. , 1997, Science.

[68]  Sietsema Wk,et al.  The absolute oral bioavailability of selected drugs , 1989 .

[69]  G. Kéri,et al.  High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. , 2004, Molecular pharmacology.

[70]  H. Varmus,et al.  Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain , 2005, PLoS medicine.

[71]  A. Levitzki,et al.  Tyrosine kinase inhibition: an approach to drug development. , 1995, Science.

[72]  J. Goldman Tyrosine-kinase inhibition in treatment of chronic myeloid leukaemia , 2000, The Lancet.

[73]  W. Miller,et al.  Inhibition of insulin-like growth factor I receptor autophosphorylation by novel 6-5 ring-fused compounds. , 2004, Biochemical pharmacology.

[74]  T. Kennedy Managing the drug discovery/development interface , 1997 .

[75]  J. Tsukada,et al.  Effect of YM087, a potent nonpeptide vasopressin antagonist, on vasopressin-induced protein synthesis in neonatal rat cardiomyocyte. , 1998, Cardiovascular research.

[76]  Stephen S. Taylor,et al.  Aurora-kinase inhibitors as anticancer agents , 2004, Nature Reviews Cancer.

[77]  Chi Ma,et al.  JNK inhibition as a potential strategy in treating Parkinson's disease. , 2004, Drug news & perspectives.

[78]  Nguyen-Huu Xuong,et al.  Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase. , 1999 .

[79]  D. Birnbaum,et al.  BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. , 1991, Oncogene.

[80]  Balázs Sarkadi,et al.  The role of ABC transporters in drug resistance, metabolism and toxicity. , 2004, Current drug delivery.

[81]  H. Kantarjian,et al.  Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. , 2004, Blood.

[82]  Olle Stål,et al.  Akt kinases in breast cancer and the results of adjuvant therapy , 2003, Breast Cancer Research.

[83]  Michael S. Cohen,et al.  Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors , 2005, Science.

[84]  D. Ziegler Polyneuropathy in the diabetic patient--update on pathogenesis and management. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[85]  R. Tootell,et al.  Phase I ascending single and multiple dose studies to assess the safety, tolerability and pharmacokinetics of AZD0530, a highly selective, dual-specific Src-Abl inhibitor , 2005 .

[86]  Yusuke Nakamura,et al.  Prediction of Sensitivity to STI571 among Chronic Myeloid Leukemia Patients by Genome‐wide cDNA Microarray Analysis , 2002, Japanese journal of cancer research : Gann.

[87]  J. R. Peterson,et al.  Autoinhibited proteins as promising drug targets , 2004, Journal of cellular biochemistry.

[88]  K. Resing,et al.  Lessons in Rational Drug Design for Protein Kinases , 2005, Science.

[89]  Alexander Levitzki,et al.  Protein tyrosine kinase inhibitors as novel therapeutic agents. , 1999, Pharmacology & therapeutics.

[90]  S. Chong,et al.  P-glycoprotein plays a role in the oral absorption of BMS-387032, a potent cyclin-dependent kinase 2 inhibitor, in rats , 2005, Cancer Chemotherapy and Pharmacology.

[91]  Max Dobler,et al.  5D-QSAR: the key for simulating induced fit? , 2002, Journal of medicinal chemistry.

[92]  John Kuriyan,et al.  Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). , 2001, Cancer research.

[93]  A. Levitzki Targeting signal transduction for disease therapy. , 1996, Current opinion in cell biology.

[94]  Jerry L. Adams,et al.  2,4,5- triarylimidazole inhibitors of IL-1 biosynthesis , 1995 .

[95]  G. Müller,et al.  Medicinal chemistry of target family-directed masterkeys. , 2003, Drug discovery today.

[96]  J. Madwed,et al.  Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate. , 2002, Journal of medicinal chemistry.

[97]  B. Druker,et al.  RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518. , 2005, Blood.

[98]  B G Benson,et al.  Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. , 2001, Science.

[99]  A. Ullrich,et al.  Proteomic characterization of the angiogenesis inhibitor SU6668 reveals multiple impacts on cellular kinase signaling. , 2005, Cancer research.

[100]  H. van de Waterbeemd,et al.  ADMET in silico modelling: towards prediction paradise? , 2003, Nature reviews. Drug discovery.

[101]  Khai Pang Leong,et al.  Tyrosine kinase inhibitors: a new approach for asthma. , 2004, Biochimica et biophysica acta.

[102]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[103]  P. Seeburg,et al.  Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. , 2000, Science.

[104]  B. Druker,et al.  Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970. , 2004, Blood.

[105]  B. Curry,et al.  ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. , 2002, Cancer research.

[106]  Hiroshi Yasui,et al.  Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. , 2005, Blood.

[107]  J. Lisnock,et al.  The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. , 2003, Chemistry & biology.

[108]  K. Watanabe,et al.  Specific inhibitors of tyrosine-specific protein kinases: properties of 4-hydroxycinnamamide derivatives in vitro. , 1989, Cancer research.

[109]  A. Vulpetti,et al.  Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. , 2005, Journal of medicinal chemistry.

[110]  P. Cohen,et al.  Specificity and mechanism of action of some commonly used protein kinase inhibitors , 2000 .

[111]  B D Silverman,et al.  Comparative molecular moment analysis (CoMMA): 3D-QSAR without molecular superposition. , 1996, Journal of medicinal chemistry.

[112]  A. Levitzki,et al.  Signal-transduction therapy. A novel approach to disease management. , 1994, European journal of biochemistry.

[113]  R. Kalluri Basement membranes: structure, assembly and role in tumour angiogenesis , 2003, Nature reviews. Cancer.

[114]  Hiroshi Hirai,et al.  Recent advances in the development of selective small molecule inhibitors for cyclin-dependent kinases. , 2005, Current topics in medicinal chemistry.

[115]  Brian K Shoichet,et al.  Kinase inhibitors: not just for kinases anymore. , 2003, Journal of medicinal chemistry.

[116]  A. Ullrich,et al.  HER2/neu: a target for breast cancer therapy. , 2000, Breast disease.

[117]  R. Bohacek,et al.  Novel protein kinase inhibitors: SMART drug design technology. , 2003, BioTechniques.

[118]  G. Alton,et al.  Therapeutic modulation of inflammatory gene transcription by kinase inhibitors , 2002, Expert opinion on biological therapy.

[119]  Jerry L. Adams,et al.  A protein kinase involved in the regulation of inflammatory cytokine biosynthesis , 1994, Nature.

[120]  Brian Schryver,et al.  A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers , 1998, The EMBO journal.

[121]  Alex Matter,et al.  Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug , 2002, Nature Reviews Drug Discovery.

[122]  M. Kan,et al.  Expression of fibroblast growth factor‐1 (FGF‐1), FGF‐2 and FGF receptor‐1 in a human salivary‐gland adenocarcinoma cell line: Evidence of autocrine growth , 1996 .

[123]  B. Klebl Chemical kinomics - a target gene family approach in chemical biology. , 2004, Drug discovery today. Technologies.

[124]  Anthony C. Bishop,et al.  Structural basis for selective inhibition of Src family kinases by PP1. , 1999, Chemistry & biology.

[125]  M. Vieth,et al.  Kinomics-structural biology and chemogenomics of kinase inhibitors and targets. , 2004, Biochimica et biophysica acta.

[126]  Doris Hafenbradl,et al.  Drug discovery in the kinase inhibitory field using the Nested Chemical Library technology. , 2005, Assay and drug development technologies.

[127]  A. Levitzki,et al.  Development of New Insulin-like Growth Factor-1 Receptor Kinase Inhibitors Using Catechol Mimics* , 2003, Journal of Biological Chemistry.

[128]  H. Hurwitz,et al.  Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[129]  A. Ullrich,et al.  Strategies to overcome resistance to targeted protein kinase inhibitors , 2004, Nature Reviews Drug Discovery.

[130]  A. Ullrich,et al.  Mutation of Threonine 766 in the Epidermal Growth Factor Receptor Reveals a Hotspot for Resistance Formation against Selective Tyrosine Kinase Inhibitors* , 2003, The Journal of Biological Chemistry.

[131]  A. Vedani,et al.  Combining protein modeling and 6D-QSAR. Simulating the binding of structurally diverse ligands to the estrogen receptor. , 2005, Journal of medicinal chemistry.

[132]  Ligand-based QSAR Studies on the Indolinones Derivatives as Inhibitors of the Protein Tyrosine Kinase of Fibroblast Growth Factor Receptor by CoMFA and CoMSIA , 2004 .

[133]  P. Casellas,et al.  SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. , 1998, The Journal of pharmacology and experimental therapeutics.

[134]  S. Doggrell BMS-354825: a novel drug with potential for the treatment of imatinib-resistant chronic myeloid leukaemia , 2005, Expert opinion on investigational drugs.

[135]  G Beck,et al.  Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. , 2001, Journal of pharmaceutical sciences.

[136]  D. Moscatelli,et al.  Expression of fibroblast growth factors and their receptors in acquired immunodeficiency syndrome—associated Kaposi sarcoma tissue and derived cells , 1993, Cancer.

[137]  P. Lollini,et al.  Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. , 2005, Cancer research.

[138]  M. Bogoyevitch,et al.  Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. , 2004, Biochimica et biophysica acta.

[139]  G. Müller,et al.  Second-generation kinase inhibitors , 2005, Expert opinion on therapeutic targets.

[140]  M. Cotten,et al.  Chemical Proteomic Analysis Reveals Alternative Modes of Action for Pyrido[2,3-d]pyrimidine Kinase Inhibitors* , 2004, Molecular & Cellular Proteomics.

[141]  J. Kuriyan,et al.  The Conformational Plasticity of Protein Kinases , 2002, Cell.

[142]  P. Sismondi,et al.  FGFRI and PLAT genes and DNA amplification at 8p 12 in breast and ovarian cancers , 1993, Genes, chromosomes & cancer.

[143]  Haddad Jj VX-745. Vertex Pharmaceuticals. , 2001 .

[144]  L. Toledo,et al.  Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors. , 2000, Structure.

[145]  R. Martell,et al.  Phase I study of BMS-599626, an oral pan-HER tyrosine kinase inhibitor, in patients with advanced solid tumors , 2005 .

[146]  H Briem,et al.  Multiple-conformation and protonation-state representation in 4D-QSAR: the neurokinin-1 receptor system. , 2000, Journal of medicinal chemistry.

[147]  R. Nilakantan,et al.  Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents. , 2002, Bioorganic & medicinal chemistry letters.

[148]  M. Baccarani,et al.  New tyrosine kinase inhibitors in chronic myeloid leukemia. , 2005, Haematologica.

[149]  Bhabatosh Chaudhuri,et al.  Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. , 2002, Pharmacology & therapeutics.

[150]  J. Pines,et al.  Cyclins and cyclin-dependent kinases: take your partners , 1993 .

[151]  M. Lamers,et al.  Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine. , 1999, Journal of molecular biology.

[152]  I Kövesdi,et al.  Reliability of logP predictions based on calculated molecular descriptors: a critical review. , 2002, Current medicinal chemistry.

[153]  K. Shokat,et al.  Novel chemical genetic approaches to the discovery of signal transduction inhibitors. , 2002, Drug discovery today.

[154]  M. Meyerson,et al.  EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. , 2005, The New England journal of medicine.

[155]  S. Shaltiel,et al.  Mapping the ATP‐Binding Site in the Catalytic Subunit of A denosine‐3′:5′‐monophosphate‐Dependent Protein Kinase , 1978 .

[156]  L. Tong,et al.  A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket , 1997, Nature Structural Biology.

[157]  Philip R. Cohen,et al.  Use of a drug‐resistant mutant of stress‐activated protein kinase 2a/p38 to validate the in vivo specificity of SB 203580 , 1999, FEBS letters.

[158]  Domenico Coppola,et al.  Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[159]  R. Panek,et al.  In vitro biological characterization and antiangiogenic effects of PD 166866, a selective inhibitor of the FGF-1 receptor tyrosine kinase. , 1998, The Journal of pharmacology and experimental therapeutics.

[160]  E. Sausville,et al.  Identification of cytosolic aldehyde dehydrogenase 1 from non‐small cell lung carcinomas as a flavopiridol‐binding protein , 1999, FEBS letters.

[161]  N. Lemoine,et al.  Expression and functional activity of fibroblast growth factors and their receptors in human pancreatic cancer , 1994, International journal of cancer.

[162]  Toshimasa Tanaka,et al.  Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent. , 2005, Journal of medicinal chemistry.

[163]  Jun Sano,et al.  Centrosomal Kinases, HsAIRK1 and HsAIRK3, are Overexpressed in Primary Colorectal Cancers , 2000, Japanese journal of cancer research : Gann.

[164]  G. Kéri,et al.  Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib). , 2005, Cancer research.

[165]  William Pao,et al.  Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[166]  J. Bruner,et al.  Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[167]  Thomas Lengauer,et al.  A fast flexible docking method using an incremental construction algorithm. , 1996, Journal of molecular biology.

[168]  R. Knegtel,et al.  Crystal Structure of Aurora-2, an Oncogenic Serine/Threonine Kinase* , 2002, The Journal of Biological Chemistry.

[169]  J. Sebolt-Leopold,et al.  CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). , 2003, Seminars in oncology.

[170]  J. Wityak,et al.  MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. , 1998, Bioorganic & medicinal chemistry letters.

[171]  Cherrington,et al.  SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. , 2000, Cancer research.

[172]  Pascal Furet,et al.  Tyrosine kinase inhibitors: From rational design to clinical trials , 2001, Medicinal research reviews.

[173]  Story Mt Regulation of prostate growth by fibroblast growth factors. , 1995 .

[174]  R. Huber,et al.  Design and crystal structures of protein kinase B-selective inhibitors in complex with protein kinase A and mutants. , 2005, Journal of medicinal chemistry.

[175]  David Bebbington,et al.  VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo , 2004, Nature Medicine.

[176]  A. Ullrich,et al.  Protein tyrosine kinase Syk modulates EGFR signalling in human mammary epithelial cells. , 2004, Cellular signalling.

[177]  J. Zheng,et al.  Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. , 1991, Science.

[178]  A. Bridges,et al.  A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. , 1994, Science.

[179]  E. Meltzer,et al.  An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. , 2005, The Journal of allergy and clinical immunology.

[180]  Willem Soudijn,et al.  Allosteric modulation of G protein-coupled receptors: perspectives and recent developments. , 2004, Drug discovery today.

[181]  J. Baselga,et al.  HER-Targeted Tyrosine-Kinase Inhibitors , 2002, Oncology.

[182]  Pierre Hubert,et al.  Tyrosine kinase receptors as attractive targets of cancer therapy. , 2004, Critical reviews in oncology/hematology.

[183]  S. Barry,et al.  AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. , 2005, Cancer research.

[184]  S. McLeskey,et al.  The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells , 2000, Nature.

[185]  Philip R. Cohen,et al.  PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in Vivo(*) , 1995, The Journal of Biological Chemistry.