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Lead Candidates (lead + candidate)

Distribution by Scientific Domains
Chemistry40%

Selected Abstracts

Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery process

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2002
Philip R. Tiller
Throughput for early discovery drug metabolism studies can be increased with the concomitant acquisition of metabolite screening information and quantitative analysis using ultra-fast gradient chromatographic methods. Typical ultra-fast high-performance liquid chromatography (HPLC) parameters used during early discovery pharmacokinetic (PK) studies, for example, employ full-linear gradients over 1,2,min at very high flow rates (1.5,2,mL/min) on very short HPLC columns (2,×,20,mm). These conditions increase sample throughput by reducing analytical run time without sacrificing chromatographic integrity and may be used to analyze samples generated from a variety of in vitro and in vivo studies. This approach allows acquisition of more information about a lead candidate while maintaining rapid analytical turn-around time. Some examples of this approach are discussed in further detail. Copyright © 2002 John Wiley & Sons, Ltd. [source]

In-vitro and in-vivo assays for angiogenesis-modulating drug discovery and development

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2006
Michelle W. Phung
In the past 35 years, significant findings have been made in relation to angiogenesis, and how this usually normal physiological function is converted into an abnormal state in cancer. To search for agents that can inhibit angiogenesis, and thereby prevent a tumour from proliferation and spread that is ultimately fatal to the patient, various in-vitro assays have been developed. In addition, older assays have been refined usually into high throughput screening formats, mainly by the biopharmaceutical industry in their attempts to develop novel therapeutic molecules and maintain a pipeline of lead candidates. The central aim is to extract more accurate data that would facilitate the birth of innovative mechanisms to defeat aberrant angiogenesis in-vivo. At the same time, better in-vivo models have been established, with the goal to mimic as close as possible the natural progression of various types of neoplasms in response to a good angiogenic response. More clinically relevant models are needed as anti-angiogenesis drug discovery and drug development companies fast track their lead molecules from preclinical investigations to phase I clinical trials. [source]

High-resolution biomarker discovery: Moving from large-scale proteome profiling to quantitative validation of lead candidates

PROTEOMICS - CLINICAL APPLICATIONS, Issue 10-11 2008
Johannes A. Hewel
Abstract Diverse proteomic techniques based on protein MS have been introduced to systematically characterize protein perturbations associated with disease. Progress in clinical proteomics is essential for personalized medicine, wherein treatments will be tailored to individual needs based on patient stratification using noninvasive disease monitoring procedures to reveal the most appropriate therapeutic targets. However, breakthroughs await the successful development and application of a robust proteomic pipeline capable of identifying and rigorously assessing the relevance of multiple candidate proteins as informative diagnostic and prognostic indicators or suitable drug targets involved in a pathological process. While steady progress has been made toward more comprehensive proteome profiling, the emphasis must now shift from in depth screening of reference samples to stringent quantitative validation of selected lead candidates in a broader clinical context. Here, we present an overview of the emerging proteomic strategies for high-throughput protein detection focused primarily on targeted MS/MS as the basis for biomarker verification in large clinical cohorts. We discuss the conceptual promise and practical pitfalls of these methods in terms of achieving higher dynamic range, higher throughput, and more reliable quantification, highlighting research avenues that merit additional inquiry. [source]

Target-Family-Oriented Focused Libraries for Kinases,Conceptual Design Aspects and Commercial Availability

CHEMBIOCHEM, Issue 3 2005
Olaf Prien Dr.
Tailor-made libraries may increase the likelihood of identifying potential lead candidates in early drug-discovery phases. That at least 12 commercial vendors offer their services in providing compound collections of tentative kinase inhibitors reflects the growing interest in kinases within the pharmaceutical industry. Some conceptual design approaches for focused library design for the kinase family are reviewed, and the design concepts of these commercialized libraries is discussed. [source]