Vol. 6 No. 2B June 2001

IPK'2001

2ND INTERNATIONAL CONFERENCE ON INHIBITORS OF PROTEIN KINASES

(DESIGN * STRUCTURAL BIOLOGY * PHOSPHORYLATION/DEPHOSPHORYLATION * BIOCHEMISTRY * BIOTECHNOLOGY * CLINICAL ASPECTS * CHEMOTHERAPY)

AND

WORKSHOP ON COMPUTER-AIDED DRUG DESIGN

SEPTEMBER 9-15, 2001, WARSAW, POLAND

INTERNATIONAL ADVISORY BOARD:

DIRK BOSSEMEYER (GERMANY)
PHILIP COHEN (UK)
WILLIAM A. DENNY (NEW ZEALAND)
YASUO FUKAMI (JAPAN)
BRIAN A. HEMMINGS (SWITZERLAND)
LOUISE N. JOHNSON (UK)
EDWIN G. KREBS (USA)
DAVID S. LAWRENCE (USA)
ALEXANDER LEVITZKY (ISRAEL)
J. ANDREW MCCAMMON (USA)
EISUKE NISHIDA (JAPAN)
LORENZO A. PINNA (ITALY)
SUSAN S. TAYLOR (USA)

ORGANIZED BY:

ICM, WARSAW UNIVERSITY
INSTITUTE OF BIOCHEMISTRY & BIOPHYSICS, PAS, WARSAW
COMMITTEE OF BIOCHEMISTRY & BIOPHYSICS, PAS, WARSAW
INTERNATIONAL INSTITUTE OF MOLECULAR & CELL BIOLOGY, WARSAW

UNDER THE AUSPICES OF THE

INTERNATIONAL UNION OF BIOCHEMISTRY AND MOLECULAR BIOLOGY (IUBMB)
AND
INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY (ICGEB)


Volume 6 (2001) pp 448
Title PREFACE
Authors David Shugar
 

Protein phosphorylation is widely recognized as the most important pathway of regulation of protein functions in living cells, by switching cellular activities from one state to another, and regulating gene expression, cell proliferation and cell differentiation. It is the major mechanism by which cells respond to extracellular signals such as hormones and growth factors, and controls all events at various stages of the cell cycle. Reversible protein phosphorylation is catalyzed by protein kinases and protein phosphatases. Dysfunctions in activities of protein kinases may lead to severe pathological states, and it is consequently not surprising that many biotechnology companies have for some time been "targeting" these enzymes as potentially important targets for drug development.

The foregoing led to the organization, in September, 1998, of the 1st International Conference on INHIBITORS OF PROTEIN KINASES (IPK'98), followed by publication of all the invited lectures, each in the form of an overview, in the journal PHARMACOLOGY & HERAPEUTICS, Vol. 82 (Nos. 2-3), 1999. In the intervening three years, there has been unabated remarkable progress in identification and specificities of protein kinases, their three-dimensional structures and mechanisms of action, delineation of signaling pathways, in many instances with the aid of inhibitors, and numerous promising applications of the latter as therapeutic agents. This prompted us to undertake the organization of the present 2nd such Conference, which is truly international in scope, and involves participation of leading specialists, representing a broad range of disciplines, from both academia and the biotechnological industry.

We are indebted to the Editors of this journal for undertaking publication of the Abstracts of invited lecturers, and of posters accepted for presentation (including some selected for short oral presentation). Also listed are Abstracts of invited lectures, and posters, to be presented at an accompanying Workshop on Molecular Modelling Techniques, including applications to protein kinases.

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Volume 6 (2001) pp 449-556
Abstracts of the lectures
Abstracts List p38 MAP KINASE INHIBITORS:FROM BIOCHEMICAL TOOLS TO CLINICAL TRIALS
Jerry L. Adams, Michael J. Bower, Jeffrey C. Boehm, Timothy F. Gallagher, Ralph Hall, Baoguang Zhao and John C. Lee - p450

PROTEIN KINASE INHIBITORS AND ANTIBIOTIC RESISTANCE
Albert M. Berghuis - p 452

STRUCTURAL ASPECTS OF PROTEIN KINASE CONTROL
Richard A. Engh and Dirk Bossemeyer - p453

HOW TO CURE DIABETES WITHOUT CAUSING CANCER
Philip Cohen - p454

CHEMICAL APPROACHES TO PROTEIN PHOSPHORYLATION
Philip A. Cole - p456

SMALL MOLECULE IRREVERSIBLE INHIBITORS OF THE erbB FAMILY OF TRANSMEMBRANE RECEPTORS
William A. Denny - p457

HIGHLY SPECIFIC AND MEMBRANE PERMEANT PEPTIDE INHIBITORS OF cGMP-DEPENDENT PROTEIN KINASE Ia
Wolfgang R.G. Dostmann, Christian K. Nickl, Mark S. Taylor, Joseph E. Brayden, Ronald Frank and Werner J. Tegge - p458

PROTEIN KINASES AS TARGETS FOR ANTICANCER AGENTS: FROM INHIBITORS TO USEFUL DRUGS
Doriano Fabbro - p459

EGFR KINASE INHIBITION: IT'S ROLE IN DIVERSE DISEASES
Philip Frost - p462

INHIBITION AND ACTIVATION OF c-Src: THE HEAD AND TAIL OF A COIN
Yasuo Fukami - p463

USE OF PROTEIN KINASE INHIBITORS TO DISSECT THE REGULATION OF PROTEIN KINASE B (PKB/Akt) BY UPSTREAM KINASES
Michelle M. Hill, Mirjana Andjelkovic, Derek P. Brazil, Stefano Ferrari, Doriano Fabbro and Brian A. Hemmings - p465

MOLECULAR RECOGNITION AND ACTIVE SITE STRUCTURE IN PHOSPHORELAY SIGNAL TRANSDUCTION
James A. Hoch - p466

ESTABLISHMENT OF A BINDING ASSAY FOR PROTEIN KINASE C (PKC) ISOZYMES USING SYNTHETIC C1 PEPTIDES AND DEVELOPMENT OF NEW MEDICINAL LEADS WITH PKC ISOZYME AND C1 DOMAIN SELECTIVITY
Kazuhiro Irie - p467

STRUCTURE BASED DESIGN OF A POTENT INHIBITOR OF CDK2
Tom G. Davies, Jane A. Endicott, Louise N. Johnson, Martin E. M. Noble, Christine E. Arris, Joe Bentley, A. Hilary Calvert, Nicola J. Curtin, Bernard T. Golding, Roger J. Griffin, Ian H. Hardcastle, Veronique Mesguiche, Herbie Newell, Roger J. Parsons, Hayley J. Whitfield, Tom Boyle and Philip Jewsbury - p470

GENOME WIDE SCREENING FOR INHIBITORS OF PROTEIN KINASES
Stephen M. Mccraith and Michael Kahn - p471

FROM CONSENSUS SEQUENCE TO HIGH AFFINITY LIGANDS: ACQUISITION OF SIGNALING PROTEIN MODULATORS
David Lawrence - p472

PATHOLOGICAL ANGIOGENESIS: MOLECULAR ASPECTS AND THERAPEUTIC INHIBITION OF ENDOTHELIAL RECEPTOR TYROSINE KINASES
Dieter Marme - p473

PHARMACOLOGICAL MANIPULATION OF Rho-ASSOCIATED KINASE, ROCK
Shuh Narumiya - p476

DOCKING INTERACTIONS IN THE MAP KINASE CASCADES
Takuji Tanoue and Eisuke Nishida - p477

CYCLIN DEPENDENT KINASES AS A POTENTIAL THERAPEUTIC TARGET FOR STROKE
David S. Park - p478

STRUCTURAL BASIS FOR THE ACTIVITY OF pp60c-src PROTEIN TYROSINE KINASE INHIBITORS
Montgomery Pettitt - p479

STRUCTURAL BASIS FOR SELECTIVE INHIBITION OF PROTEIN KINASE CK2 BY ATP SITE-DIRECTED LIGANDS
Stefania Sarno, Roberto Battistutta, Erika De Moliner, Flavio Meggio, Giuseppe Zanotti and Lorenzo A. Pinna - p480

GSK-3; A COMMON TARGET OF EXTRACELLULAR STIMULI AND SELECTIVE SMALL MOLECULE INHIBITORS THAT MODULATE GLYCOGEN METABOLISM AND NEURONAL DEATH
Alastair D. Reith -p482

NOVEL AND SPECIFIC Rho-KINASE INHIBITOR, H1152P, DIRECTED AGAINST THE Rho-KINASE INVOLVED PATHWAY
Yasuharu Sasaki, Mami Ikenoya, Naoki Yamamoto, Masaaki Suzuki and Hiroyoshi Hidaka - p483

DISCOVERY OF SUBSTRATES AND SMALL MOLECULE INHIBITORS FOR A DEATH ASSOCIATED PROTEIN KINASE
Anastasia V. Velentza, Andrew M. Schumacher, Curtis Weiss, Anu Sawkar, Magdalena Zasadzki, Jacques Haiech, Martin Egli and D. Martin Watterson - p484

DESIGNING SPECIFIC PROTEIN KINASE INHIBITORS: INSIGHTS FROM COMPUTER SIMULATIONS AND COMPARATIVE SEQUENCE/STRUCTURE ANALYSIS
Chung F. Wong - p486

MODULATION OF PROTEIN KINASE SIGNALING BY PROTEIN PHOSPHATASES AND INHIBITORS
Zhong-Yin Zhang - p487

Poster Abstracts
Abstracts List BIOCHEMICAL AND FUNCTIONAL ANALYSIS OF STK DURING HEAD REGENERATION IN HYDRA
Marcela Cí Rdenas M., Yanko Fabila and Luis M. Salgado

EXTRACELLULAR SIGNAL-REGULATED KINASE 1/2 IS A DEFENSE MECHANISM FOR NEURONS EXPOSED TO DNA-DAMAGE
Agata Goźdź, Marcin Chlystun and Michał Hetman

NATURAL VERSUS SYNTHETIC GENISTEIN IN A DRUG DEVELOPMENT PERSPECTIVE
Grzegorz Grynkiewicz

GLYCOGEN SYNTHASE KINASE-3b AS A TARGET FOR ANTI- APOPTOTIC SIGNALS
Michał Hetman, Agata Kaleta, Marcin Chłystun, Matthew Higgins, Jane Cavanaugh and Zhengui Xia

INHIBITION OF LYN KINASE POTENTIATES BCR-MEDIATED SIGNALING AND PROLIFERATION
Scott Jakes, Susan Lukas, Brian Castle, Roger Snow, Neil Moss and Marilyn Kehry

PHOSPHORYLATION OF CALCYCLIN BINDING PROTEIN (CacyBP)
Beata Jastrzębska, Anna Filipek and Jacek Kuźnicki

EFFECT OF INHIBITORS OF POLYPEPTIDE GROWTH FACTOR RECEPTOR TYROSINE KINASE ON ATP SYNTHESIS IN PLASMA MEMBRANES OF HUMAN MALIGNANT TUMORS
V.S. Demidova, A.G. Globa and Arthur A. Karelin

EFFECT OF FIBRATES ON BRANCHED CHAIN a-KETOACID DEHYDROGENASE (BCKDH) KINASE ACTIVITY
Malgorzata Knapik-Czajka, Izabela Cyganek, Pawel Wołkow and Jerzy Jaskiewicz

SOLVENT BEHAVIOR IN THE MOLECULAR DYNAMICS SIMULATIONS OF FREE Cdk2 AND ITS COMPLEXES WITH INHIBITORS
Zdenek Kŕiž, Michal Otyepka and Jaroslav Koča

EFFECT OF INHIBITORS AGAINST THE MAPK AND PI3K PATHWAYS ON HEAD REGENERATION OF HYDRA
G. Cecilia Manuel, Asdrubal Aguilera and Luis M. Salgado

MOLECULAR FEATURES OF SELECTIVE POLYPHENOLIC INHIBITORS OF PROTEIN KINASE CK2
Flavio Meggio, Stefano Moro, Arianna Donella Deana, Diego Dal Ben, Stefania Sarno, Giuseppe Zagotto and Lorenzo A. Pinna

NOVEL AND SPECIFIC RHO-KINASE INHIBITOR, H1152P, DIRECTED AGAINST THE RHO-KINASE INVOLVED PATHWAY
Yasuharu Sasaki, Mami Ikenoy, Naoki Yamamoto, Masaaki Suzuki and Hiroyoshi Hidaka

TUMOR-PROMOTING PHORBOL ESTERS BIND DIRECTLY TO THE REGULATORY DOMAIN OF DIACYLGLYCEROL KINASE GAMMA
Mayumi Shindo, Kazuhiro Irie, Hajime Ohigashi, Masamitsu Kuriyama and Naoaki Saito

INTERACTION OF PALMITOYLCARNITINE WITH PROTEIN KINASE C IN NEUROBLASTOMA NB-2a CELLS
Joanna Sobiesiak-Mirska, Maciej J. Nalecz and Katarzyna A. Nalecz

PHOSPHORYLATION OF RAF-1 BY KINASE SUPPRESSOR OF RAS (KSR-1) IS INHIBITED BY ”MEK-SPECIFIC’ INHIBITORS PD 098059 AND U0126 IN DIFFERENTIATING HL60 CELLS
Xuening Wang and George P. Studzinski

THE KINETIC MECHANISM OF THE PHOSPHORYLATION OF A MODEL FOR A TRANSCRIPTION FACTOR SUBSTRATE BY ERK2
William F. Waas and Kevin N. Dalby

ENZYME-LINKED IMMUNOSORBENT ASSAY FOR DETERMINATION OF P21-ACTIVATED KINASE ACTIVITY
Jau-Song Yu, Sheng-Hung Chang, Wen-Hsiung Chan and Hua-Chien Chen

Abstracts of Oral Presenations
Abstracts List STRUCTURAL AND THERMODYNAMIC VALIDATION OF INACTIVE CDK2 AS A TEMPLATE FOR STRUCTURE-BASED DRUG DESIGN
Thomas G. Davies, Jane A. Endicott, Martin E. M. Noble, Louise N. Johnson, Christine E. Arris, Johanne Bentley, F. Thomas Boyle, A. Hilary Calvert, Nicola J. Curtin, Philip J. Jewsbury, Ashley E. Gibson, Bernard T.Golding, Roger J. Griffin, Ian Hardcastle, Vernonique Mesguiche, Rachael Parsons, Hayley Whitfield and David R. Newell

TOWARDS A PKB INHIBITOR
Shoshana Klein, Tamar Geiger, Hadas Reuven, Nurit Livnah and Alexander Levitzki

A NEW CLASS OF p38 MAP KINASE INHIBITORS THAT EXPLOIT A NOVEL BINDING SITE
Neil Moss, Steffen Breitfelder, Pier Cirillo, Thomas Gilmore, Anne Graham, Eugene Hickey, Jeffrey Madwed, Monica Moriak, Chris Pargellis, Alfred Proto, John Regan, Alan Swinamer, Liang Tong and Carol Torcellini

IDENTIFICATION OF THE AUTOINHIBITORY DOMAIN OF PKN: CONSTRUCTION OF A SELECTIVE INHIBITOR OF THE PKN FAMILY
Hideyuki Mukai and Yoshitaka Ono

MOLECULAR DYNAMICS STUDY ON FREE cdk2 AND ITS COMPLEXES WITH PURINE-LIKE INHIBITORS
Michal Otyepka, Zdenek Kŕiž and Jaroslav Koča

2 INTEGRIN-LINKED KINASE 1 (ILK1): A "HOT" THERAPEUTIC TARGET
Penny C. Costell1, D. Ljiljana Kojic, Mojgan Jabali, Zaihui Zhang, Ladan Azli, Nathan Yoganathan, Dan Leung, Jun Yan, Arthur Yee, Shoukat Dedhar, Jasbinder Sanghera

A NOVEL CHEMICAL GENETIC APPROACH FOR V-SRC SUBSTRATES REVEALS ORDERED ASSEMBLY OF RETROGRADE SIGNALLING PATHWAY
Kavita Shah

THE DISCOVERY OF 2-PHENYLAMINO-IMIDAZO[4,5-h]ISO- QUINOLIN-9-ONES, A NEW CLASS OF INHIBITORS of Lck KINASE WITH in vivo ACTIVITY
Roger J. Snow, Tanja Butz, Mario G. Cardozo, Robert J. Eckner, Daniel R. Goldberg, Abdelhakim Hammach, Scott Jakes, Suresh Kapadia, Susan Lukas, Tina M. Morwick, Neil Moss, Maret Panzenbeck, Usha R. Patel, Gregory W. Peet, Jeffrey D. Peterson, Anthony S. Prokopowicz Iii, Hidenori Takahashi, Jonathan D. Tan, Matt A. Tschantz, Xiao-Jun Wang and Rosemarie Zinter

BIBX 1382, A SELECTIVE EGFR TYROSINE KINASE INHIBITOR, INHIBITS CELL PROLIFERATION, INDUCES CELL DIFFERENTIATION AND DISPLAYS ANTI-TUMOR ACTIVITY AGAINST A VARIETY OF XENOGRAFT MODELS
Flavio F. Solca, Guenther Adolf, Horst Ahorn, Anke Baum, Georg Dahmann, Frank Hilberg, Frank Himmelsbach, Thomas Metz and Jacques Van Meel

SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS FOR SOLUBLE 6-SUBSTITUTED 4-ANILINOQUINOLINE-3- CARBONITRILES. ORALLY ACTIVE, IRREVERSIBLE INHIBITORS OF THE TYROSINE KINASE ACTIVITY OF THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)
Hwei-Ru Tsou, Elsebe Overbeek, Marvin F. Reich, M. Brawner Floyd, Bernard D. Johnson, Brian C. Gruber, Fei Ye, William A. Hallett, Ramaswamy Nilakantan, Ru Shen, Yu-Fen Wang, Lee M. Greenberger and Allan Wissner

WORKSHOP on MOLECULAR MODELING METHODS
Invited Lectures
Abstracts List CAN HOMOLOGY MODELS BE USED FOR HIGH THROUGHPUT DOCKING? KINASES AS A TEST CASE
Hugues-Olivier Bertrand

PROTEIN IONIZATION STATE PREDICTION USING A POISSON- BOLTZMANN METHOD
James M. Briggs

PREDICTION OF RATES OF ENCOUNTER OF A SMALL MOLECULE WITH A PROTEIN USING A BROWNIAN DYNAMICS METHOD IN A CONTINUUM SOLVENT ENVIRONMENT
James M. Briggs

NEW LEADS FOR DRUG DEVELOPMENT FROM VIRTUAL SCREENING
Gerhard Klebe

DOCKING STRATEGIES: BINDING OF SUBSTRATE AND INHIBITORS TO S-ADENOSLYHOMOCYSTEINE HYDROLASE “ A CASE STUDY
Krzysztof Kuczera, Yongbo Hu, Dan Yin and Ronald T. Borchardt

FREE ENERGY SIMULATIONS APPLIED TO BIOCHEMICAL PROBLEMS
Krzysztof Kuczera

SIMPLE MODEL FOR LIGAND - MACROMOLECULE INTERACTIONS
Witold R. Rudnicki and Krzysztof Ginalski

DOCKING AND SCORING. EXPLORING THE LIMITATIONS OF UNDERSTANDING MOLECULAR RECOGNITION
Michal Vieth

MODELING DRUG-RECEPTOR INTERACTIONS STARTING FROM THE SEQUENCE OF A RECEPTOR
Chung F. Wong

WORKSHOP on MOLECULAR MODELING METHODS
Posters
Abstracts List HOMOLOGY-DERIVED THREE-DIMENSIONAL STRUCTURE PREDICTION OF FERULOYL ESTERASE FROM ASPERGILLUS NIGER
Fraj O. Aliwan, Richard Pickersgill and Gary Williamson

DYNAMIC PHARMACOPHORE MODEL DEVELOPMENT AND TESTING
James M. Briggs, Maria Letizia Barreca, Jinxia Deng, Matthew Lee, Keun Woo Lee and Adeyemi Adesokan

MOLECULAR DYNAMICS STUDIES AND STRUCTURAL ANALYSES OF ALANINE RACEMASE - AS A DRUG DESIGN TARGET
James M. Briggs, Gabriela Iurcu Mustata, Hung-Chung Huang and Thereza A. Soares

MODELLING THE 3D STRUCTURE OF PROTEIN KINASE C g AND ITS INTERACTION WITH SPECIFIC INHIBITOR, CHELERYTHRINE
Pawel Brodacki, Krzysztof Ginalski and Bogdan Lesyng

QUANTUM-MECHANICAL CALCULATIONS OF THE POTENTIAL ENERGY FUNCTION FOR THE PHOSPHATE TRANSFER IN MODEL
SYSTEMS Krzysztof Ginalski, Pawel Grochowski and Bogdan Lesyng

ONKOGENIC ACTIVATION CAUSED BY POINT MUTATIONS IN THE KINASE DOMAIN OF THE MET PROTO-ONCOGENE: MOLECULAR MODELING STUDIES
Maria Miller, Krzysztof Ginalski, Bogdan Lesyng, Noboru Nakaigawa, Laura Schmidt and Berton Zbar

MOLECULAR RECOGNITION IN KINASES THROUGH COMPUTATIONAL CHEMISTRY
Michal Vieth

PREDICTION OF PROTONATION STATES OF PHOSPHOTYROSINE IN SHORT PEPTIDES AND PROTEINS
Michal Wojciechowski, Tomasz Grycuk, Jan Antosiewicz and Bogdan Lesyng

Ser/Thr PROTEIN PHOSPHATASE-1 AND -2A CATALYTIC UNITS: SIMULATION OF THEIR INTERACTIONS WITH SELECTED SUBSTATE AND INHIBITOR SEQUENCES
Edyta Woźniak-Celmer, Stanisław Ołdziej and Jerzy Ciarkowski

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