Chemical genomics: a challenge for de novo drug design

Dean, Philip M.

doi:10.1007/s12033-007-0037-x

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…Molecules-In this study, a preconstituted library, composed of bicyclic peptidomimetics, bicycles from tartaric acid and amino acids (BTAa), 3 was used for assays on selected yeast strains (supplemental Table 1 First Level Assays-First level assays allowed the selection of a restricted number of active molecules. W303 and 0117 strains were grown in YPD.…”

Section: Methodsmentioning

confidence: 99%

“…New approaches emerging from chemical and biological knowledge, such as "chemical genetics" (2), consist of the study of biological systems by systematic investigation of the effects of small molecules on a specific cellular model rather than perturbing with gene mutations (3)(4)(5). This new approach has been divided into forward and reverse chemical genetics; the former is based on the research of a desired phenotypic effect following the administration of small molecules to biological systems of interest, whereas the latter is based on the investigation of the effects of small molecules against a specific target (6 -8).…”

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confidence: 99%

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A Systems Biology Approach to Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants

Stefanini

Trabocchi

Marchi

et al. 2010

Journal of Biological Chemistry

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In recent years, an approach called "chemical genetics" has been adopted in drug research to discover and validate new targets and to identify and optimize leads by high throughput screening. In this work, we tested the ability of a library of small peptidomimetics to induce phenotypic effects with functional implications on a panel of strains of the budding yeast Saccharomyces cerevisiae, both wild type and mutants, for respiratory function and multidrug resistance. Further elucidation of the function of these peptidomimetics was assessed by testing the effects of the compound with the most prominent inhibitory activity, 089, on gene expression using DNA microarrays. Pathway analysis showed the involvement of such a molecule in inducing oxidative damage through alterations in mitochondrial functions. Transcriptional experiments were confirmed by increased levels of ROS and activation of mitochondrial membrane potential. Our results demonstrate the influence of a functional HAP1 gene in the performance of S. cerevisiae as a model system.Pharmaceutical and biotechnological fields are constantly looking for new drugs characterized by innovation and economy (1). New approaches emerging from chemical and biological knowledge, such as "chemical genetics" (2), consist of the study of biological systems by systematic investigation of the effects of small molecules on a specific cellular model rather than perturbing with gene mutations (3-5). This new approach has been divided into forward and reverse chemical genetics; the former is based on the research of a desired phenotypic effect following the administration of small molecules to biological systems of interest, whereas the latter is based on the investigation of the effects of small molecules against a specific target (6 -8). To make these new approaches time-and moneysaving, the set-up of easy, rapid, and economical chemical synthesis and biological screening processes is essential (9, 10). The budding yeast Saccharomyces cerevisiae, which has been defined as an "honorary mammal" (11), is a suitable model organism for this aim, mainly because of the high degree of conservation with human cells concerning main biological processes (11). Thanks to its ease of manipulation, it can be successfully used to identify molecules of pharmacological interest (4, 12). Moreover, once active compounds have been selected, functional information about their mode of action can be inferred from screening ϳ5000 viable yeast haploid deletion mutant strains for hypersensitivity or hyperresistance to each molecule, thus identifying pathways that influence the cellular response to tested compounds (13-16). However, so far, chemical genetic approaches have used only one genetic background, that of laboratory strain S288c, which is limited by an accumulation of genetic defects, such as the inability to sustain proper respiratory metabolism of this strain (4,(17)(18)(19). In this work, we selected a panel of strains in which it is possible to investigate the influence of a library of mole...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

A Systems Biology Approach to Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants

Stefanini

Trabocchi

Marchi

et al. 2010

Journal of Biological Chemistry

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“…Thus, the issues raised through the interest in computational biology, bioinformatics and systems biology are translated into a more beneficial information involving a more complicated task of data interpretation. Several wealthy nations have divided their budgets allocating some portions of it to novel insights of pharmacogenomics since massive developments in genomic designs must be pushed through along with its trade value in the market [19] . The biotechnology field that follows the combined concepts of bioinformatics and genomics through the pharmaceutical product development of pharmacogenomics is crucial for the study of genomic function.…”

Section: Dissentmentioning

confidence: 99%

Management in quantum revenue architectures for EPC probability modelling of travaux preparatoires on corporate crimes based on economic legal fiction of excise tax

Llarena¹

2022

Int. J. Res. Hum. Resour. Manage.

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Every government system follows the principle of ultimate powers in divided authorities responsible to promote public welfare and safety through constitutional practice of economic freedom. Pharmacoeconomics deals with cost-effective analysis in alignment with administrative functions of the government in relation to ethical behavior of private companies to comply with the rules and regulations expressed by the legislation and its comparative parliamentary legal system for guidance and control of appropriate ethical conduct as advocated by warranty issues of intellectual property. The intended design of PDE-5 inhibitors for marketing their products for public use as medication is indicated in their patent registration as strict compliance of advocating patient safety. Public funds are used by the government to advocate cost-effective analysis in pharmacoeconomics. Therefore, direct taxation of product services and practice of health promotion must be properly addressed and coordination in aligning the institutional goals with employment law for proper compliance of handling patented products. Furthermore, indirect taxation based on public funds must resolve issues concerning taxes collected from private companies handling patented drug products with clear specification of intended design for patient efficacy and safety. Corporate Governance is a conceptual framework of business designs intended to illustrate the various activities of a company towards fulfilling its profit goals as private stakeholder and contributing to public interests for social obligation of sustainable development. Disclosure of corporate social responsibility is the central mechanism of corporate governance. Based on stakeholder theory, corporate governance strongly influences corporate social responsibility disclosure to enhance the relationship of stakeholders and its business community. Tax aggressiveness is utilized by board director and its members to lessen tax contribution which is contrary to the government sector goals of maximizing tax impositions for public welfare and safety. Unlawful behavior on tax aggressiveness is known as tax evasion while tax avoidance is not a violation and serves as a loophole to the taxation system. UNCITRAL model law is a legal arbitration concept of making "commercial" expand to other comparable jurisdiction of international trade. The European Patent Commission is the legal authority that delineates medical policies from patented products. Travaux preparatoires is a design practice within legal context of restricted jurisdiction for commercial exercise of strict liability. This paper aims to develop arbitration framework based on stakeholder theory of corporate governance to explain the correlation of tax planning with patented products and medical processes involving therapeutic, surgical, and veterinary policies. Therefore, tax evasion is not apparent criminal behavior and tax planning on medical policies and patented drugs must have a separate strategic means of increasing monetary success for tax...

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“…DNID approach is applied for designing where no inhibitors were reported previously [113,114]. In DNID, the ligand is built based upon the complementarity of the active site in a target with the ligand [115,116]. A webserver named "Drugster" has implemented LigBuilder for building ligands.…”

Section: Software Descriptionmentioning

confidence: 99%

Open Source Software and Web Services for Designing Therapeutic Molecules

Singla

Dhanda²,

Chauhan³

et al. 2013

CTMC

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Despite the tremendous progress in the field of drug designing, discovering a new drug molecule is still a challenging task. Drug discovery and development is a costly, time consuming and complex process that requires millions of dollar and 10-15 years to bring new drug molecules in the market. This huge investment and long-term process are attributed to high failure rate, complexity of the problem and strict regulatory rules, in addition to other factors. Given the availability of 'big' data with ever improving computing power, it is now possible to model systems which is expected to provide time and cost effectiveness to drug discovery process. Computer Aided Drug Designing (CADD) has emerged as a fast alternative method to bring down the cost involved in discovering a new drug. In past, numerous computer programs have been developed across the globe to assist the researchers working in the field of drug discovery. Broadly, these programs can be classified in three categories, freeware, shareware and commercial software. In this review, we have described freeware or open-source software that are commonly used for designing therapeutic molecules. Major emphasis will be on software and web services in the field of chemo- or pharmaco-informatics that includes in silico tools used for computing molecular descriptors, inhibitors designing against drug targets, building QSAR models, and ADMET properties.

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Chemical genomics: a challenge for de novo drug design

Cited by 6 publications

References 22 publications

A Systems Biology Approach to Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants

A Systems Biology Approach to Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants

Management in quantum revenue architectures for EPC probability modelling of travaux preparatoires on corporate crimes based on economic legal fiction of excise tax

Open Source Software and Web Services for Designing Therapeutic Molecules

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