https://www.science.org/content/blog-post/rare-silicon-switch 
Here’s another example of an idea that has been kicking around for years in medicinal chemistry without ever really breaking through: substituting a silicon atom for a carbon. To be fair, most of the time this doesn’t seem to do all that much, while introducing various uncertainties around ADME and toxicity (since we don’t have all that much experience with organosilanes as drugs). So you can see why we’re not overrun with “silyl switch” compounds. But at the same time, there really do seem to be instances where it can help.
 
For instance, there was (is?) a camptothecin derivative, known variously as karenitecin, cositecan, or BNP1350, that had an alkylsilyl side chain that was claimed to help it be less prone to being removed by efflux pumps. As far as I can tell, this one has kicked around in a number of Phase I and II trials without ever advancing. And a silane analog of haloperidol did indeed show a different (and quite possibly beneficial) metabolic profile, but I don’t think that one even made it to the clinic. As I mentioned in that blog post linked in the first paragraph, I sent in a trimethylsilyl-for-t-butyl switch compound one time in an analoging program, and I have to say that the response from the project team was not a favorable one. But as often happens, there seemed to be no particular advantage to the TMS analog, so it didn’t become an issue, other than in the “Please don’t do that again” way.
 
This new paper (first link in the post) is a silyl-containing KIF18A kinesin inhibitor, which is class of compounds with several representatives, some of which are in the clinic already for susceptible cancers. Like the example mentioned above, this switch (a silapiperidine for plain piperidine) seems to have improved efflux stability. I’m not completely sure how this occurs, though - the silicon analogs are a big less hydrophilic, but what efflux transport proteins like and dislike is still a mystery to me (and no, not just to me!) 
 
I find it hard to believe that “silicon slows down efflux pumping” will turn out to be a general rule, but I think it’s an idea that’s worth testing if your particular project is having that sort of trouble. Just be ready for some pushback! We’ll see if this compound (ATX020) advances. The company behind it (Accent Therapeutics) is calling it a “tool compound”, but we’ll see if they have the nerve (or the need!) to take a similar organosilane into human trials. . .
https://www.science.org/content/blog-post/rare-silicon-switch