[drmilsurp]

Lot's of things we think we know but don't and chemical space is super large? Why a molecule works within a mouse but not human, depends on what you mean by doesn't work. It might not be that it doesn't work but that the potential drug never makes it that far in the process for other reasons. Common reasons would be poor ADMET issues and difficulty in formulation for enteral route.

edit for other route Al Mann spent almost a billion and 20 years on inhalable insulin and only recently found success.

Also, works is a matter of interpretation. Better relative to other drugs on the market? Shows better outcomes than no treatment? There are some drugs out there that with time and more investigation are showing some lack of efficacy, eg gliptins