So basically we work on small molecules for anti-cancer therapy in our lab (one aspect). The problem is that the molecules we're working on look promising in-vitro, but have absolutely horrendous issues with things like water solubility, being too lipophilic, and more likely than not, will be easily metabolized and excreted before it will even get into plasma. The only problem is that everyone in the lab seems to want to ignore the writing on the wall, just so they can continue to do research or not admit that what they're doing is going to fail. Nobody wants to listen, and they continue to crank out horribly designed compound after compound that, yes, each have interesting biological activity, but stand no chance of getting out of test tubes and into an organism. Not being water soluble is a huge liability, how exactly are we supposed to give our compounds to a living organism? Injection will be extremely difficult, and if you start trying to use excipients like cyclodextrins to help forumulate our compounds into something that can be given IV, you run the risk of running through a field of landmines with IP issues. Not to mention IV drugs cost much more to administer than something orally administered. If we try to give our stuff orally, the compound is going to have very poor bioavailability it looks like and it is also looking like it is going to be easily chewed up by CYP enzymes (not to mention massive doses that will need to be given that would probably cost $200,000 per dose). What would you do in this situation? Speak up, point out the huge gaping flaws in our research, and become enemy no. 1 in lab and also have your PI find you annoying, or just shut up and design the best in vitro compounds ever that in all likelihood will 0 translational use and write lower impact research?