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/)
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.
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.