Drug lead identification

The mixing of information resources to transform data into information, and information into knowledge, for the intended propose of making better decisions faster in the arena of drug lead identification and optimization. (Brown, 1998)... 

Use of Activity-based Probes for Drug Lead Identification and Assessment of Selectivity... 

Morra, G.> Genoni, A., Neves, M. A., Merz, K. M., Jr., 8c Colombo, G (2010) Molecular recognition and drug-lead identification What can molecular simulations tell us Current Medicinal Chemistry, 17, 25. 

The major impetus for the development of solid phase synthesis centers around applications in combinatorial chemistry. The notion that new drug leads and catalysts can be discovered in a high tiuoughput fashion has been demonstrated many times over as is evidenced from the number of publications that have arisen (see references at the end of this chapter). A number of )proaches to combinatorial chemistry exist. These include the split-mix method, serial techniques and parallel methods to generate libraries of compounds. The advances in combinatorial chemistry are also accompani by sophisticated methods in deconvolution and identification of compounds from libraries. In a number of cases, innovative hardware and software has been developed tor these purposes. 

Klebe G. Lead identification in post-genomics computers as a complementary alternative. Drug Discov Today Technol 2004 1 225-30. 

In the realm of drug discovery, the detection and characterization of target-ligand interactions is a critical process for lead identification, validation, and optimization. 

Abstract High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identification of leads is an essential part of drug discovery. Many factors contribute to the quality of a lead, including biological, physicochemical, ADME, and PK parameters. The identification of high quality leads, which are needed for successful lead optimization, requires the optimization of all of these parameters. Parallel optimization of all parameters is the most efficient way to achieve the goal of lead identification. 

Drug candidates that are intended for oral dosing need to have good ADME properties so that they can be dosed once or twice daily. The drug should be well absorbed, survive first pass metabolism, and have sufficiently low clearance. At the lead identification stage, the primary in vitro ADME assays employed are those that assess permeability and metabolic stability. There are a variety of assays available for both parameters, as described in the previous chapter. 

The identification of compounds with a desired property is a central pursuit in science. In the field of drug discovery combinatorial chemistry has played an increasingly important role for identification and optimization of drug leads which target therapeutically important biomolecules. For the successful implementation of combinatorial methods, new and innovative synthesis methods have been developed. Additionally, novel conceptual approaches to the design of compounds have been pursued to more efficiently generate libraries of small molecules. 

Drug development is a long and cost-intensive business. Only after years of lead identification, chemical optimization, in vitro and animal testing can the first clinical trials be conducted. Unfortunately, many projects still fail in this late stage of development after a considerable amount of money has been spent. According to estimates, preapproval costs for a new drug exceed US 800 million [1]. 

High-throughput drug-like property profiling is increasingly used during lead identification and candidate selection. HTS pharmaceutical profiling may include ... 

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