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Biomedical subjects

H Kubinyi

Publications and source records attributed to H Kubinyi.

At least 19 recordsLinked to original sources
PubMed2006

Chemogenomics in drug discovery.

Chemogenomics is a new strategy in drug discovery which, in principle, searches for all molecules that are capable of interacting with any biological target. Because of the almost infinite number of drug-like organic molecules, this is an impossible task. Therefore chemogenomics has been defined as the investigation of classes of compounds (libraries) against families of functionally related proteins. In this definition, chemogenomics deals with the systematic analysis of chemical-biological interactions. Congeneric series of chemical analogs are probes to investigate their action on specific target classes, e.g., GPCRs, kinases, phosphodiesterases, ion channels, serine proteases, and others. Whereas such a strategy developed in pharmaceutical industry almost 20 years ago, it is now more systematically applied in the search for target- and subtype-specific ligands. The term "privileged structures" has been defined for scaffolds, such as the benzodiazepines, which very often produce biologically active analogs in a target family, in this case in the class of G-protein-coupled receptors. The SOSA approach is a strategy to modify the selectivity of biologically active compounds, generating new drug candidates from the side activities of therapeutically used drugs.

Animals↗
PubMed2001

IBC's Drug Discovery Technology - Europe 2001. 23-26 April 2001, Stuttgart, Germany.

Specific sectors within the pharmaceutical industry are rapidly changing in response to technological advances. Genomics, high-throughput automated chemistry, high-throughput screening (HTS), ADME/Tox screening and informatics, provide new opportunities, but also create new bottlenecks. In addition, the selection and validation of biological targets, the proper design of compound libraries, data and knowledge management, and as the last and crucial step, the proof of therapeutic relevance by clinical trials, generates an enormous financial load on biotechnology and pharmaceutical companies. In the future, drug development costs might be reduced due to an ongoing pressure for shorter development cycles of new drugs. IBC's Drug Discovery Technology Europe 2001 conference addressed many aspects relevant to drug discovery technologies, and, along with its US partner conference, provides an annual meeting place for researchers and company executives to interact and exchange ideas.

Journal Article↗
PubMed2001

HTS Technologies--IBC Informa Conference.

In 1997, approximately US $6 billion were spent on worldwide screening technologies. The estimate for the total global market for high-throughput screening (HTS) products and services was about US $1.5 billion (source: Medical and Healthcare Marketplace Guide, 15th Edition, 1999-2000). Genomics and combinatorial chemistry demand a technological shift away from present-day laboratory to fully automated HTS and ultra HTS (uHTS), with over 100,000 compounds screened per day. The potential of new technology in miniaturization and automation will ensure faster and cheaper solutions to discovery. The conference explored the rapidly advancing field of HTS and examined numerous areas of HTS application. Identification and prioritization of viable targets, and the development of 'information rich' screens without reducing screening capacity, are important topics. Furthermore, the essential integration of all these screening, analytical and parallel synthesis systems in one coherent process is considered to be of significant interest. Focused sessions addressed the rapidly advancing areas of ADME (absorption, distribution, metabolism, elimination), toxicity and formulation screening, including virtual 'in silico' screening.

Journal Article↗
PubMed1999

ACS Award for Computers in Chemical and Pharmaceutical Research.

A one-day symposium honored Corwin H Hansch (Pomona College, Claremont, CA, USA), who received the ACS Award for Computers in Chemical and Pharmaceutical Research. Helen M Free (Board of Directors, American Chemical Society) presented the award "for his pioneering work in 1962 in initiating a generalized mathematical means for relating chemical structure to biological activity. This paradigm, now called Quantitative Structure Activity Relationships (QSAR), wields tremendous importance today in drug and pesticide research, environmental toxicology, and biochemistry".

Journal Article↗
PubMed1998

A scoring scheme for discriminating between drugs and nondrugs.

A scoring scheme for the rapid and automatic classification of molecules into drugs and nondrugs was developed. The method is a valuable new tool that can aid in the selection and prioritization of compounds from large compound collections for purchase or biological testing and that can replace a considerable amount of laborious manual work by a more unbiased approach. It is based on the extraction of knowledge from large databases of drugs and nondrugs. The method was set up by using atom type descriptors for encoding the molecular structures and by training a feedforward neural network for classifying the molecules. It was parametrized and validated by using large databases of drugs and nondrugs (169 331 molecules from the Available Chemicals Directory, ACD, and 38 416 molecules from the World Drug Index, WDI). The method revealed features in the molecular descriptors that either qualify or disqualify a molecule for being a drug and classified 83% of the ACD and 77% of the WDI adequately.

Databases, Factual↗
PubMed1998

Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from SEAL similarity matrices.

The program SEAL is suited to describe the electrostatic, steric, hydrophobic, and hydrogen bond donor and acceptor similarity of different molecules in a quantitative manner. Similarity scores AF can be calculated for pairs of molecules, using either a certain molecular property or a sum of weighted properties. Alternatively, their mutual similarity can be derived from distances d or covariances c between SEAL-based property fields that are calculated in a regular grid. For a set of N chemically related molecules, such values form an N x N similarity matrix which can be correlated with biological activities, using either regression analysis and an appropriate variable selection procedure or partial least-squares (PLS) analysis. For the Cramer steroid data set, the test set predictivities (r2pred = 0.53-0.84) of different PLS models, based on a weighted sum of molecular properties, are superior to published results of CoMFA and CoMSIA studies (r2pred = 0.31-0.40), regardless of whether a common alignment or individual, pairwise alignments of all molecules are used in the calculation of the similarity matrices. Training and test set selections have a significant influence on the external predictivities of the models. Although the SEAL similarity score between two molecules is a single number, its value is based on the 3D properties of both molecules. The term 3D quantitative similarity-activity analyses (3D QSiAR) is proposed for approaches which correlate 3D structure-derived similarity matrices with biological activities.

Drug Design↗
PubMed1998

Strategies and techniques for identification of novel bioactive compounds--CHI's second annual conference. 7-9 October 1998, Zurich, Switzerland.

This conference on recent developments in the discovery of novel therapeutic candidates was organized by Amy Dasch (Cambridge Healthtech Institute, Newton Upper Falls, MA, USA; http://www.xensei.com/conferences). The conference provided an overview of all relevant aspects of the rapidly changing paradigms in drug research. Gene technology creates a vast number of new biological targets. The progress in combinatorial chemistry and high-throughput screening (HTS) is accompanied by the development of virtual libraries, large screening programs, and the generation of enormous sets of data. Correspondingly, the lectures covered such different topics as target identification and assay development, HTS technology, combinatorial library design and synthesis, chemoinformatics, and the integration of these components into the discovery of novel pharmaceutical compounds, the development of agricultural chemicals, and other applications. A most valuable addition was reports on case histories in drug development from pharmaceutical companies utilizing these technologies. About 100 scientists, many of them from European countries, attended the meeting. In total, 25 lectures were presented in four sessions: molecular diversity and library design; combinatorial synthesis; HTS; computational methodologies and chemoinformatics. Like other commercially organized conferences, this meeting was well-planned. The balance of speakers from small venture capital companies, large pharmaceutical and agricultural firms gave a broad overview of recent progress in the rational design, combinatorial synthesis, and HTS of new bioactive compounds, as well as on different approaches to handling large data sets and deriving structure-activity relationships from such data.

Journal Article↗
PubMed1995

Strategies and recent technologies in drug discovery.

In the last years, the paradigms of drug research changed significantly. New technologies were developed, in several different fields. Combinatorial chemistry and high-throughput screening increase our chances to find new lead structures, with less effort than by dedicated syntheses. Gene technology, in addition to providing therapeutically useful proteins, significantly contributes to rational drug design. The primary structure of a protein can be derived from the DNA sequence of the corresponding gene. Its relevance for a certain disease is investigated in transgenic animals. Expression of the protein in bacteria or in cell culture produces material for screening systems and for 3D structure determination by protein crystallography. NMR techniques, or electron cryo-microscopy. Structure-based and computer-aided design methods are applied to optimize lead structures with the least effort. A serious problem in the application of such techniques is their limitation to ligand-protein interactions. For the design of a therapeutically useful drug, also absorption, distribution, metabolism and elimination have to be considered. QSAR methods help in this respect. Scope and limitations of the new technologies are discussed in the context of conventional approaches in drug discovery.

Animals↗