Note that a number of well-known drugs violate Lipinski's rules. For instance, digoxin is absorbed by transporters and violates 2 rules. Atorvastatin is another famous example (again 2 rules violated). I believe that it is absorbed through Peyer's patches in the intestine.

https://www.pmf.ni.ac.rs/chemianaissensis/wp-content/uploads...

Thanks for pointing it out. The Wikipedia article mentions that as well, along with some other examples:

> Some authors have criticized the rule of five for the implicit assumption that passive diffusion is the only important mechanism for the entry of drugs into cells, ignoring the role of transporters.

> Studies have also demonstrated that some natural products break the chemical rules used in Lipinski filters such as macrolides and peptides.

thanks for sharing these exceptions.

key quote from the linked wikipedia article:

This famous "rule of 5" has been highly influential in this regard, but only about 50% of orally administered new chemical entities actually obey it. [5]

[5] O Hagan S, Swainston N, Handl J, Kell DB (2015). "A 'rule of 0.5' for the metabolite-likeness of approved pharmaceutical drugs". Metabolomics. 11 (2): 323–339. doi:10.1007/s11306-014-0733-z. PMC 4342520. PMID 25750602.

it's more like guidelines than a rule.