Conclusions

Much progress has been made in the last decade in the development and clinical use of antimetabolites as chemotherapeutics for the treatment of solid tumors. Both mono- and combination therapies have been found to be efficacious, and clinical trials are under way to determine efficacies against a greater variety of tumor types, and of regimens involving two-, three-, and four-drug combinations. Toxicities associated with the therapies have spurred investigation into methods of diagnosing tumors by expression levels of targeted enzymes, to increase the likelihood of efficacy in specific patient populations. As for continued discovery of antimetabolite oncolytics, new chemical entities in this class are not reported as frequently as in the period 1985-95 in the peer-reviewed medicinal chemistry literature, as interest appears to have shifted to the development of kinase inhibitors rather than cytotoxic agents as 'targeted therapies' for carcinomas, lymphomas, and leukemias. Nonetheless, many antimetabolites are the standards of care in oncology, and are likely to remain so for several years to come.

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Biographies

Mary M Mader, PhD, earned her bachelor's degree in chemistry in 1985 from the Ohio State University and then worked for a year as a structure editor at Chemical Abstracts Service. She received her doctorate in organic chemistry from the University of Notre Dame in 1991. As a NIH postdoctoral fellow at the University of California-Berkeley, she pursued the computer-aided design and synthesis of peptidic thioacetal inhibitors of cysteine proteases. From 1993 to 1999 she served as a faculty member at Grinnell College and was promoted to the rank of associate professor in 1999. Her research with undergraduate scientists centered on synthetic methods and computational analysis of organosilane oxidations. Dr Mader joined Eli Lilly in 2000 and has been active in the discovery of kinase inhibitors for the cardiovascular, inflammation, and oncology therapeutic areas.

J R Henry received a bachelor's degree from Virginia Tech in 1989, and a PhD in organic chemistry in 1994 from The Pennsylvania State University under the direction of Prof Steven Weinreb. After an NIH postdoctoral fellowship with Prof Andrew Kende at The University of Rochester, he joined the Drug Discovery group at the R W Johnson Pharmaceutical Research Institute in Raritan, NJ as a medicinal chemist. During this time, his efforts were focused on the design of novel p38 MAP kinase inhibitors for the treatment of inflammatory diseases. In 2000, he moved to his current position at Eli Lilly where he is a Principal Research Scientist. His research continues to focus on the design and synthesis of novel kinase inhibitors for a variety of diseases, primarily cancer.

© 2007 Elsevier Ltd. All Rights Reserved Comprehensive Medicinal Chemistry II

No part of this publication may be reproduced, stored in any retrieval system or transmitted ISBN (set): 0-08-044513-6 in any form by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers ISBN (Volume 7) 0-08-044520-9; pp. 55-79

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