Unknown

Dataset Information

0

Phenocopy--a strategy to qualify chemical compounds during hit-to-lead and/or lead optimization.

ABSTRACT: A phenocopy is defined as an environmentally induced phenotype of one individual which is identical to the genotype-determined phenotype of another individual. The phenocopy phenomenon has been translated to the drug discovery process as phenotypes produced by the treatment of biological systems with new chemical entities (NCE) may resemble environmentally induced phenotypic modifications. Various new chemical entities exerting inhibition of the kinase activity of Transforming Growth Factor ? Receptor I (TGF-?R1) were qualified by high-throughput RNA expression profiling. This chemical genomics approach resulted in a precise time-dependent insight to the TGF-? biology and allowed furthermore a comprehensive analysis of each NCE's off-target effects. The evaluation of off-target effects by the phenocopy approach allows a more accurate and integrated view on optimized compounds, supplementing classical biological evaluation parameters such as potency and selectivity. It has therefore the potential to become a novel method for ranking compounds during various drug discovery phases.

SUBMITTER: Baum P 

PROVIDER: S-EPMC3000806 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

A phenocopy is defined as an environmentally induced phenotype of one individual which is identical to the genotype-determined phenotype of another individual. The phenocopy phenomenon has been translated to the drug discovery process as phenotypes produced by the treatment of biological systems with new chemical entities (NCE) may resemble environmentally induced phenotypic modifications. Various new chemical entities exerting inhibition of the kinase activity of Transforming Growth Factor β Re  ...[more]

Similar Datasets

Other Small Molecule PCSK9 Inhibitors: Hit to lead optimization
2018-06-20 | GSE110426 | GEO
Unknown Protocol for hit-to-lead optimization of compounds by auto <i>in silico</i> ligand directing evolution (AILDE) approach.
| S-EPMC7856476 | biostudies-literature
Unknown Hit-to-Lead Optimization of Benzoxazepinoindazoles As Human African Trypanosomiasis Therapeutics.
| S-EPMC8329730 | biostudies-literature
Unknown Hit-to-lead and lead optimization binding free energy calculations for G protein-coupled receptors.
| S-EPMC7653344 | biostudies-literature
Unknown Hit-to-lead optimization of novel benzimidazole phenylacetamides as broad spectrum trypanosomacides.
| S-EPMC7578707 | biostudies-literature
Genomics Small Molecule PCSK9 Inhibitors: Hit to lead optimization
| PRJNA433685 | ENA
Unknown Structural simplification: an efficient strategy in lead optimization.
| S-EPMC6804494 | biostudies-literature
Unknown Combining computational methods for hit to lead optimization in Mycobacterium tuberculosis drug discovery.
| S-EPMC3946937 | biostudies-literature
Unknown Discovery and Hit-to-Lead Optimization of Non-ATP Competitive MK2 (MAPKAPK2) Inhibitors.
| S-EPMC4017987 | biostudies-literature
Unknown Hit-to-lead optimization of a benzene sulfonamide series for potential antileishmanial agents.
| S-EPMC8126888 | biostudies-literature