The amino terminal domain of steroid hormone receptors as a novel drug target: Identification of small molecule inhibitors

2016 ◽  
Author(s):  
Amy E. Monaghan ◽  
Stuart McElroy ◽  
Iain J. McEwan
Keyword(s):  
Small Molecule ◽  
Drug Target ◽  
Hormone Receptors ◽  
Target Identification ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Amino Terminal ◽  
Drug Target Identification ◽  
Amino Terminal Domain ◽  
Novel Drug

scholarly journals Treponema pallidumPutative Novel Drug Target Identification and Validation: Rethinking Syphilis Therapeutics with Plant-Derived Terpenoids

2015 ◽  
Vol 19 (2) ◽  
pp. 104-114 ◽  
Author(s):  
Upendra N. Dwivedi ◽  
Sameeksha Tiwari ◽  
Priyanka Singh ◽  
Swati Singh ◽  
Manika Awasthi ◽  
...  
Keyword(s):  
Drug Target ◽  
Target Identification ◽  
Drug Target Identification ◽  
Novel Drug

Photo-cross-linked small-molecule affinity matrix as a tool for target identification of bioactive small molecules

2016 ◽  
Vol 33 (5) ◽  
pp. 709-718 ◽  
Author(s):  
Naoki Kanoh
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Drug Target ◽  
Target Identification ◽  
Affinity Matrix ◽  
Industrial Chemical ◽  
Drug Target Identification ◽  
The Status

This review describes the status of the photo-cross-linked small-molecule affinity matrix while providing a useful tutorial for academic and industrial chemical biologists who are involved or interested in drug target identification.

Drug-target identification in Drosophila cells: combining high-throughout RNAi and small-molecule screens

2007 ◽  
Vol 12 (1-2) ◽  
pp. 28-33 ◽  
Author(s):  
Norbert Perrimon ◽  
Adam Friedman ◽  
Bernard Mathey-Prevot ◽  
Ulrike S. Eggert
Keyword(s):  
Small Molecule ◽  
Drug Target ◽  
Target Identification ◽  
Drug Target Identification ◽  
Drosophila Cells

scholarly journals LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes

2019 ◽  
Author(s):  
Ilaria Piazza ◽  
Nigel Beaton ◽  
Roland Bruderer ◽  
Thomas Knobloch ◽  
Crystel Barbisan ◽  
...  
Keyword(s):  
Small Molecule ◽  
Binding Sites ◽  
Drug Target ◽  
Drug Targets ◽  
Target Identification ◽  
Limited Proteolysis ◽  
Drug Binding ◽  
Homologous Proteins ◽  
Protein Targets ◽  
Drug Target Identification

Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in developing optimized small-molecule compounds. Current unbiased approaches cannot directly pinpoint the interaction surfaces between ligands and protein targets. To address his limitation we have developed a new drug target deconvolution approach based on limited proteolysis coupled with mass spectrometry that works across species including human cells (LiP-Quant). LiP-Quant features an automated data analysis pipeline and peptide-level resolution for the identification of any small-molecule binding sites, Here we demonstrate drug target identification by LiP-Quant across compound classes, including compounds targeting kinases and phosphatases. We demonstrate that LiP-Quant estimates the half maximal effective concentration (EC50) of compound binding sites in whole cell lysates. LiP-Quant identifies targets of both selective and promiscuous drugs and correctly discriminates drug binding to homologous proteins. We finally show that the LiP-Quant technology identifies targets of a novel research compound of biotechnological interest.

scholarly journals Small molecule photocatalysis enables drug target identification via energy transfer

2021 ◽  
Author(s):  
Aaron D Trowbridge ◽  
Ciaran P Seath ◽  
Frances P Rodriguez-Rivera ◽  
Beryl X Li ◽  
Barbara E Dul ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Drug Discovery ◽  
Small Molecule ◽  
Drug Target ◽  
Target Identification ◽  
High Energy ◽  
Therapeutic Benefit ◽  
Cellular Targets ◽  
Cellular Environment ◽  
Drug Target Identification

The identification of cellular targets that can be exploited for therapeutic benefit, broadly known as target ID, remains a fundamental goal in drug discovery. In recent years, the application of new chemical and biological technologies that accelerate target ID has become commonplace within drug discovery programs, as a complete understanding of how molecules react in a cellular environment can lead to increased binding selectivity, improved safety profiles, and clinical efficacy. Established approaches using photoaffinity labelling (PAL) are often costly and time-consuming due to poor signal-to-noise coupled with extensive probe optimization. Such challenges are exacerbated when dealing with low abundance membrane proteins or multiple protein target engagement, typically rendering target ID unfeasible. Herein, we describe a general platform for photocatalytic small molecule target ID, which hinges upon the generation of high-energy carbene intermediates via visible light-mediated Dexter energy transfer. By decoupling the reactive warhead from the drug, catalytic signal amplification results in multiple labelling events per drug, leading to unprecedented levels of target enrichment. Through the development of cell permeable photocatalyst conjugates, this method has enabled the quantitative target and off target identification of several drugs including (+)-JQ1, paclitaxel, and dasatinib. Moreover, this methodology has led to the target ID of two GPCRs, ADORA2A and GPR40m, a class of drug target seldom successfully uncovered in small molecule PAL campaigns.

STEROID HORMONE RECEPTORS AND CLINICAL RELEVANCE

1975 ◽  
Vol 80 (1_Suppla) ◽  
pp. S160-S161 ◽  
Author(s):  
H. Maass
Keyword(s):  
Clinical Relevance ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors
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