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High-throughput drug discovery is highly depended on the targets available to accelerate the process of candidates screening. Traditional chemical proteomics approaches for the screening of drug targets usually require the immobilization/modification of the drug molecules to pull down the interacting proteins. Recently energetics-based proteomics methods provide an alternative way to study drug-protein interaction by using complex cell lysate directly without any modification of the drugs. In this study, we developed a novel energetics-based proteomics strategy, solvent-induced protein precipitation (SIP) approach, to profile the interaction of drugs with their target proteins by using quantitative proteomics. The method is easy to use for any laboratory with common chemical reagents of acetone, alcohol and acetic acid. The SIP approach was able to identify the well-known protein targets of methotrexate, SNS-032 and a pan-kinase inhibitor of staurosporine in cell lysate. We further applied this approach to discover the off-targets of geldanamycin. Three known protein targets of HSP90 family were successfully identified, and several potential off-targets including NADH dehydrogenase subunits NDUFV1 and NDUFAB1 were identified for the first time, and the NDUFV1 was validated by using western blotting. In addition, this approach was capable of evaluating affinity of drug-target interaction. The data collectively proved that our approach provides a powerful platform for drug target discovery.
This article was published in the following journal.
Name: Analytical chemistry
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Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
A method which uses specific precipitation reactions to separate or collect substances from a solution.
The process of finding chemicals for potential therapeutic use.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
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Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...