Dmg discovery

Fig. 7. The cycle of stmcmie-based dmg design. The conventional or basic cycle consists of a simple loop between chemical synthesis and biological activity. This cycle is typically initiated through a lead compound. Whereas this cycle remains the core of the dmg discovery process, the resources available...

Approaches to cytotoxic chemotherapy iaclude special emphasis on dmg targeting and toxicity alleviation. The directions ia which new dmg discovery strategies are moving and the criteria used for advanciag compounds iato clinical trials (2) are discussed hereia, as are all of the dmgs approved by the United States Food and Dmg Administration (FDA) for the treatment of cancer as of this writing and those compounds ia clinical trials. 

The modem dmg discovery team consists of medicinal chemists, biologists, metaboHsm and pharmacokiaeti.es speciaHsts, and toxicologists working together to improve dmg selection. 

The catalysis of ester hydrolysis by other groups within the ester molecule (intramolecular catalysis) has been extensively studied (17,18). These reactions are important because they simulate catalysis by en2ymes. Intramolecular catalysis of esters has been used as a model in dmg discovery efforts (19). 

Jahnke W, Erlanson DA (2006) Fragment-based approaches in dmg discovery. Wiley, New York... 

Studt T Datamining tools keep you ahead of the flood. Dmg Discovery Dev 2000 August 30-36. 

Todd MD et al. Emerging technologies for accelerated toxicity evaluation of potential dmg candidates. Curr Opin Dmg Discovery Dev 1999 2 58-68. 

Bailey D, Brown D. High-throughput chemistry and structure-based design survival of the smartest. Dmg Discovery Today 2001 6 57-59. 

White RE. High-throughput screening in drug metabolism and pharmacokinetic support of dmg discovery. Annu Rev Pharmacol Toxicol 2000 40 133-157. 

These three simple observations (time, substrate and NADPH dependence) can be used to detect potential MBIs early in the dmg discovery process, as simple experiments can be designed from established screening protocols used to measure CYP... 

On the other hand, if a dmg idea does nof work, blessed are those who gave their all to see it through. In this regard, I think the following quote from Teddy Roosevelf nicely sums up the thrill of dmg discovery ... 

Olsson, T., Oprea, T.I. Cheminformatics a tool for decision-makers in dmg discovery. Curr. Opin. Drug. Disc. Dev. 2001, 4, 308-313. 

DeStevens, G. Serendipity and stmctured research in dmg discovery. Prog. Drug. Res. 1986, 30, 189-203. 

Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in dmg discovery and development settings. 

Bohacek, R.S. and Mcmartin, C. Modem computational chemistry and dmg discovery stmcture generating programs. Curr. Opin. Chem. Biol. 1997, 1, 157-161. 

Gordon, E.M., Barrett, R.W., Dower, W.J., Fodor, P.A., and Gallop, M.A. Applications of combinatorial technologies to dmg discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. /. Med. Chem. 1994, 37, 1386-1401. 

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