Lead profiling

There are a number of such relevant correlations to be always considered. Based on both relevance for lead profiling and in silica availability of molecular properties. 

Cadmium and lead profiles in birds feathers based on samples in the milligram range and below were determined by solid sampling Zeeman-GFAAS, using a feather RM produced by milling at liquid nitrogen temperatures and characterized for its metal contents with different analytical methods (Hahn et al. 1990). 

At the outset of a lead identification effort, it is imperative to establish specific criteria for potency, selectivity, ADME properties, etc. to generate a desired lead profile. This profile serves to guide the lead identification efforts based on the initial characterization of the hits. 

Criteria for biological properties may be project specific, but ADME property and physical property criteria are generally invariant. Lead profiles will be addressed in more detail in the section on parallel optimization. 

As mentioned in Sect. 3, it is important to establish a detailed lead profile at the beginning of a lead identification effort. Criteria vary in different lead identification or hit-to-lead groups, but generally include some or all of the following potency, functional activity, selectivity, MW, clogP, solubility, permeability, microsomal stability and/or hepatocyte clearance, and preliminary PK including oral bioavail-ability. An example of a lead profile for a kinase inhibitor project is illustrated in Table 1 [21],... 

Ultraviolet spectroscopy has been applied to the determination of lead and lead speciation studies [407]. Scaule and Patterson [408] used isotope dilution-mass spectrometry to determine the lead profile in the open North Pacific Ocean. 

Lead profiles in Lake Constance (Summer 81 data Sigg, 1985) and in the Pacific Ocean (1981 data Schaule and Patterson, 1981). The similar shape of these profiles despite the difference in length scales (kilometers for the ocean and meters for the lake), illustrates the influence of the atmospheric deposition on the upper layers and the scavenging of Pb(II) by the settling particles. 

Sequential drug discovery process and lead profiling. 

Genomics to Lead Development Candidate (Preclinical Lead Profile, PLP)... 

While we do not use directly the above approach in this book, many chapters remind you that hit and lead profiling is close to detective work. It is equally exciting it carries a large volume of unknown elements which can only be dealt vdth using refined tools and protocols.. But what is most rewarding in this job is that correction, or to be precise, optimization is built into it. 

Hit and Lead Profiling. Edited by Bernard Faller and Laszlo Urban Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32331-9... 

A competitive inhibition screen is often the first step in understanding the DDI potential of a NCE. The definitive assessment of inhibition is the inhibition constant (K ), which provides not only the inhibition potency but also information on the mechanism of inhibition (competitive, non-competitive). However in the hit to lead profiling environment this approach is over-complex for the question being asked, and generates far too many samples to enable rapid screening of compound series. DDI assays based upon the IC50 principle are therefore favored. The relationship between K and IC50 for a competitive inhibitor is ... 

Genetic Toxicity In Vitro Approaches for Hit and Lead Profiling... 

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