Subject: Summary: references of marketed drugs by structure-based design

From: "Renxiao Wang" <renxiao_at_med.umich.edu>
Date: Mon, 26 Jan 2004 10:42:40 -0500

Hi, CCLers!

Last week I posted a question asking for references of marketed drugs
whose invention were largely aided by structure-based design methods.
Most of the replies point to the following review article:

Larry Hardy & Antony Malikayil, The impact of structure-guided drug
design on clinical agents, Current Drug Discovery, 2003, December,
15-20. 
http://www.currentdrugdiscovery.com/2003/december.html 
This paper discussed ~40 compounds developed with SBDD, seven of them
are marketed drugs.

Here are some addtional examples: Crixivan (1,2), Viracept (3), Trusopt
(4), Zanamivir (5,6)

1. BD Dorsey, RB Levin, SL McDaniel, JP Vacca, JP Guare, PL Darke, JA 
Zugay, EA Emini, WA Schleif, JC. Quintero, JH Lin, I-W Chen, MK
Holloway, 
PMD Fitzgerald, MG. Axel, D Ostovic, PS Anderson, JR Huff. L-735,524:
The 
Design of a Potent and Orally Bioavailable HIV Protease Inhibitor. J
Med 
Chem 37:3443-3451, 1994.

2. Holloway, M. K. et al. In Computer-Aided Molecular Design, 
Reynolds, C. H. et al., Eds. ACS Symp. Series 589:36-50, 1995.

3. SW Kaldor, VJ Kalish, JF Davies, II, BV Shetty, JE Fritz, K 
Appelt, JA Burgess, KM Campanale, NY Chirgadze, DK Clawson, BA
Dressman, 
SD Hatch, DA Khalil, MB Kosa, PP Lubbehusen, MA Muesing, AK Patick, SH

Reich, KS Su, JH Tatlock. Viracept (Nelfinavir Mesylate, AG1343): A 
Potent, Orally Bioavailable Inhibitor of HIV-1 Protease. J Med Chem 
40:3979-3985, 1997.

4. J Greer, JW Erickson, JJ Baldwin, MD Varney. Application of the 
Three-Dimensional Structures of Protein Target Molecules in 
Structure-Based Drug Design J Med Chem 37:1035-1054; 1994.

5. von Itzstein, M.; Wu, W. Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.;
Jin, 
B.; Van Phan, T.; Smythe, M.; White, H. F.; Oliver, S. W.; Colman, P.
M.; 
Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V.
J.; 
Cameron, J. M.; Penn, C. R. Rational Design of Potent Sialidase-based 
Inhibitors of Influenza Virus Replication. Nature, 363, 418-423 (1993).

6. M. von Itzstein, Jeffrey C. Dyason, Stuart W. Oliver, Hume F. White,

Wen-Yang Wu, Gaik B. Kok and Michael S. Pegg, A Study of the Active
Site 
of Influenza Sialidase: An Approach to the Rational Design of Novel 
Anti-Influenza Drugs. J. Med. Chem., 39, 388-391, (1995). 

Again, thanks for all of the responses!

With best regards,

Renxiao

--------------------------------------------------------------------------------------------------
Renxiao Wang, Ph.D.
Research Investigator
Department of Internal Medicine, Hematology/Oncology Division
University of Michigan Medical School
Ann Arbor, MI 48109, U.S.A.
Tel: (734) 764-2449; Fax: (734) 764-2532
E-mail: renxiao_at_med.umich.edu
Web: http://sw8.im.med.umich.edu/~arthur/
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