zlacker

>>atomro+(OP)
Not a medical chemist, but I noticed that three AOH1996 molecules are binding to PCNA. Would it make sense to chain together three AOH1996 molecules with flexible linkers for, I don't know, increased specificity or something like that?

>>flobos+fd
Maybe. But a bigger molecule will be less soluble and less capable of getting into the cell.

>>irdc+Yf
Right! I forgot about good ol’ Lipinski: https://en.wikipedia.org/wiki/Lipinski%27s_rule_of_five

>>flobos+pm
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...

>>mallom+Ny
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.