This collection of cutting-edge reviews comprehensively examines the current status of novel antifolates, an important class of anticancer drugs. The distinguished contributors discuss the preclinical and clinical pharmacology of methotrexate, other dihydrofolate reductase inhibitors, 5-fluorouracil, and the new generation of antifolates-the thymidylate synthase and glycinamide ribonucleotide formyltransferase inhibitors. In addition, they review in depth the modulation of antifolate drugs, folate and antifolate transport mechanisms, polyglutamation, resistance, and drug combinations, as well…mehr
This collection of cutting-edge reviews comprehensively examines the current status of novel antifolates, an important class of anticancer drugs. The distinguished contributors discuss the preclinical and clinical pharmacology of methotrexate, other dihydrofolate reductase inhibitors, 5-fluorouracil, and the new generation of antifolates-the thymidylate synthase and glycinamide ribonucleotide formyltransferase inhibitors. In addition, they review in depth the modulation of antifolate drugs, folate and antifolate transport mechanisms, polyglutamation, resistance, and drug combinations, as well as pharmacogenomics, pharmacodynamics, regulation of gene expression, and mechanisms of cell death. Antifolate Drugs in Cancer Therapy provides entré to exciting new avenues for future research and constitutes a new standard reference for all basic scientists and clinicians engaged in cancer therapeutics.
Antifolate Drugs: Past and Future Perspectives Robert C. Jackson. Folate Biochemistry and Nutrition in Relation to Antifolate Selectivity Roy L. Kisliuk. Clinical Pharmacology and Resistance to Dihydrofolate Reductase Inhibitors Richard Gorlick and Joseph R. Bertino. Development of Nonpolyglutamatable Dihydrofolate Reductase (DHFR) Inhibitors Andre Rosowsky. Fluoropyrimidines as Antifolate Drugs G.J. Peters and C.H. Köhne. Raltitrexed (Tomudex(TM)) a Highly Polyglutamatable Antifolate Thymidylate Synthase Inhibitor: Design and Preclinical Activity Leslie R. Hughes Trevor C. Stephens F. Thomas Boyle and Ann L. Jackman. Tomudex: Clinical Development Philip Beale and Stephen Clarke. Preclinical Pharmacology Studies and the Clinical Development of a Novel Multitargeted Antifolate MTA (LY231514) Chuan Shih and Donald E. Thronton. GW1843: A Potent Non-competitive Thymidylate Synthase Inhibitor- Preclinical and Preliminary Clinical Studies Gary K. Smith Joseph W. Bigley Inderjit K. Dev David S. Duch Robert Ferone and William Pendergast. Preclinical and Clinical Studies with the Novel Thymidylate Synthase Inhibitor Nolatrexed Dihydrochloride (Thymitaq(TM) AG337) Andy Hughes and A. Hilary Calvert. ZD9331 F. Thomas Boyle Trevor C. Stephens S.D. Averbuch and Ann L. Jackman. Preclinical and Clinical Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitors Lometrexol and LY309887. Laurane G. Mendelsohn John F. Worzalla and Jackie M. Walling. AG2034: A GARFT Inhibitor with Selective Cytotoxicity to Cells that Lack a G1 Checkpoint Theodore J. Boritzki Cathy Zhang Chalotte A. Bartlett and Robert C. Jackson. Receptor- and Carrier-Mediated Transport Systems for Folates and Antifolates: Exploitation for Folate-Based Chemotherapy and Immunotherapy G. Jansen. Folates as Chemotherapeutic Modulators Julio Barredo Marlene A. Bunni Raghunathan Kamasamudram and David G. Priest. Antifolate Polyglutamation in Preclinical and ClinicalAntifolate Resistance John J. McGuire. Antifolates in Combination Therapy Stephen P. Ackland Madhu Garg and Rosemary Kimbell. Pharmacodynamic Measurements and Predictors of Thymidylate Synthase Inhibitors David Farrugia and Patrick G. Johnston. Moleccular Regulation of Expression of Thymidylate Synthase Edward Chu Jingfang Ju and John C. Schmitz. The Role of Uracil Misincorporation in Thymineless Death G. Wynne Aherne and Shereal Brown. Thymeineless Death Peter J. Houghton. Genetic Determinants of Cell Death and Toxicity D. Mark Pritchard and John A. Hickman. Index.
Antifolate Drugs: Past and Future Perspectives Robert C. Jackson. Folate Biochemistry and Nutrition in Relation to Antifolate Selectivity Roy L. Kisliuk. Clinical Pharmacology and Resistance to Dihydrofolate Reductase Inhibitors Richard Gorlick and Joseph R. Bertino. Development of Nonpolyglutamatable Dihydrofolate Reductase (DHFR) Inhibitors Andre Rosowsky. Fluoropyrimidines as Antifolate Drugs G.J. Peters and C.H. Köhne. Raltitrexed (Tomudex(TM)) a Highly Polyglutamatable Antifolate Thymidylate Synthase Inhibitor: Design and Preclinical Activity Leslie R. Hughes Trevor C. Stephens F. Thomas Boyle and Ann L. Jackman. Tomudex: Clinical Development Philip Beale and Stephen Clarke. Preclinical Pharmacology Studies and the Clinical Development of a Novel Multitargeted Antifolate MTA (LY231514) Chuan Shih and Donald E. Thronton. GW1843: A Potent Non-competitive Thymidylate Synthase Inhibitor- Preclinical and Preliminary Clinical Studies Gary K. Smith Joseph W. Bigley Inderjit K. Dev David S. Duch Robert Ferone and William Pendergast. Preclinical and Clinical Studies with the Novel Thymidylate Synthase Inhibitor Nolatrexed Dihydrochloride (Thymitaq(TM) AG337) Andy Hughes and A. Hilary Calvert. ZD9331 F. Thomas Boyle Trevor C. Stephens S.D. Averbuch and Ann L. Jackman. Preclinical and Clinical Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitors Lometrexol and LY309887. Laurane G. Mendelsohn John F. Worzalla and Jackie M. Walling. AG2034: A GARFT Inhibitor with Selective Cytotoxicity to Cells that Lack a G1 Checkpoint Theodore J. Boritzki Cathy Zhang Chalotte A. Bartlett and Robert C. Jackson. Receptor- and Carrier-Mediated Transport Systems for Folates and Antifolates: Exploitation for Folate-Based Chemotherapy and Immunotherapy G. Jansen. Folates as Chemotherapeutic Modulators Julio Barredo Marlene A. Bunni Raghunathan Kamasamudram and David G. Priest. Antifolate Polyglutamation in Preclinical and ClinicalAntifolate Resistance John J. McGuire. Antifolates in Combination Therapy Stephen P. Ackland Madhu Garg and Rosemary Kimbell. Pharmacodynamic Measurements and Predictors of Thymidylate Synthase Inhibitors David Farrugia and Patrick G. Johnston. Moleccular Regulation of Expression of Thymidylate Synthase Edward Chu Jingfang Ju and John C. Schmitz. The Role of Uracil Misincorporation in Thymineless Death G. Wynne Aherne and Shereal Brown. Thymeineless Death Peter J. Houghton. Genetic Determinants of Cell Death and Toxicity D. Mark Pritchard and John A. Hickman. Index.
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