4 ms·
Your point is a very important one. Do we check the interactions of a tentative drug molecule against every single molecular target in the body, and do we track
by Ezku 3y ago
Your point is a very important one. Do we check the interactions of a tentative drug molecule against every single molecular target in the body, and do we track what happens as a result of all those interactions? It’s quite common that a group of ”usual suspects” on the researchers’ radar get checked for — but by necessity, a lot of ground goes uninvestigated.
> Consider valproic acid: For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds
Speaking of ”inert” solvents:
> Dimethyl sulfoxide (DMSO) is the most common organic solvent used in biochemical and cellular assays during drug discovery programs.
> Despite its wide use, the effect of DMSO on several enzyme classes, which are crucial targets of the new therapeutic agents, are still unexplored.
> 1-4% (v/v) DMSO, the commonly used experimental concentrations, showed ∼37-80% inhibition of human acetylcholine-degrading enzyme, acetylcholinesterase (AChE)
(DMSO: A Mixed-Competitive Inhibitor of Human Acetylcholinesterase. ACS Chem Neurosci. 2017 https://pubmed.ncbi.nlm.nih.gov/29017007/ https://pubmed.ncbi.nlm.nih.gov/29017007/)
Oops! How many investigations on specific drugs were in fact showing mostly the results of what happens when interfering with one of the most ubiquitous-yet-underappreciated signalling systems, the cholinergic system?
I’m hoping widespread & systematic application of modern methods like in-silico molecular docking studies will lead to much fewer such oversights.
- _Wintermute 3y agoThat's what controls are for, you're always comparing against the DMSO control. I also don't think anyone who's doing small molecule screens thinks DMSO is inert.