Title |
Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay
|
---|---|
Published in |
Science, July 2013
|
DOI | 10.1126/science.1233606 |
Pubmed ID | |
Authors |
Daniel Martinez Molina, Rozbeh Jafari, Marina Ignatushchenko, Takahiro Seki, E. Andreas Larsson, Chen Dan, Lekshmy Sreekumar, Yihai Cao, Pär Nordlund |
Abstract |
The efficacy of therapeutics is dependent on a drug binding to its cognate target. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored inside cells. We have developed a method for evaluating drug binding to target proteins in cells and tissue samples. This cellular thermal shift assay (CETSA) is based on the biophysical principle of ligand-induced thermal stabilization of target proteins. Using this assay, we validated drug binding for a set of important clinical targets and monitored processes of drug transport and activation, off-target effects and drug resistance in cancer cell lines, as well as drug distribution in tissues. CETSA is likely to become a valuable tool for the validation and optimization of drug target engagement. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 12 | 21% |
United Kingdom | 6 | 11% |
Canada | 3 | 5% |
Netherlands | 3 | 5% |
Spain | 3 | 5% |
Australia | 2 | 4% |
Japan | 1 | 2% |
Sweden | 1 | 2% |
Paraguay | 1 | 2% |
Other | 3 | 5% |
Unknown | 22 | 39% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 40 | 70% |
Scientists | 13 | 23% |
Science communicators (journalists, bloggers, editors) | 2 | 4% |
Practitioners (doctors, other healthcare professionals) | 2 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 9 | <1% |
United Kingdom | 7 | <1% |
France | 5 | <1% |
Japan | 5 | <1% |
Netherlands | 2 | <1% |
Germany | 2 | <1% |
Singapore | 1 | <1% |
Taiwan | 1 | <1% |
Belgium | 1 | <1% |
Other | 5 | <1% |
Unknown | 1169 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 278 | 23% |
Student > Ph. D. Student | 259 | 21% |
Student > Master | 103 | 9% |
Student > Bachelor | 94 | 8% |
Student > Doctoral Student | 58 | 5% |
Other | 202 | 17% |
Unknown | 213 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 296 | 25% |
Agricultural and Biological Sciences | 240 | 20% |
Chemistry | 202 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 59 | 5% |
Medicine and Dentistry | 53 | 4% |
Other | 94 | 8% |
Unknown | 263 | 22% |