The bromodomain inhibitor (+)-JQ1 is a highly validated chemical probe; however, it exhibits poor pharmacokinetics. To guide efforts toward improving its pharmacological properties, we identified the (+)-JQ1 primary metabolite using chemical catalysis methods. Treatment of (+)-JQ1 with tetrabutylammonium decatungstate under photochemical conditions resulted in selective formation of an aldehyde at the 2-position of the thiophene ring [(+)-JQ1-CHO], which was further reduced to the 2-hydroxymethyl analog [(+)-JQ1-OH].
View Article and Find Full Text PDFThe thermal shift assay (TSA)-also known as differential scanning fluorimetry (DSF), thermofluor, and T shift-is one of the most popular biophysical screening techniques used in fragment-based ligand discovery (FBLD) to detect protein-ligand interactions. By comparing the thermal stability of a target protein in the presence and absence of a ligand, potential binders can be identified. The technique is easy to set up, has low protein consumption, and can be run on most real-time polymerase chain reaction (PCR) instruments.
View Article and Find Full Text PDFBiochim Biophys Acta Proteins Proteom
January 2021
J Chromatogr B Analyt Technol Biomed Life Sci
February 2017
The antidotal potency of dimethyl trisulfide (DMTS) against cyanide poisoning was discovered and investigated in our previous studies. Based on our results it has better efficacy than the Cyanokit and the Nithiodote therapies that are presently used against cyanide intoxication in the US. Because of their absence in the literature, the goal of this work was to develop analytical methods for determining DMTS from blood and brain that could be employed in future pharmacokinetic studies.
View Article and Find Full Text PDF