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A New Mode of Cancer Treatment

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322 points atomroflbomber | 1 comments | 03 Aug 23 08:12 UTC | HN request time: 0s | source
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flobosg ◴[03 Aug 23 09:56 UTC] No.36983634[source]▶
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?
replies(1): >>36983803 #
irdc ◴[03 Aug 23 10:21 UTC] No.36983803[source]▶
Maybe. But a bigger molecule will be less soluble and less capable of getting into the cell.
replies(1): >>36984202 #
flobosg ◴[03 Aug 23 11:18 UTC] No.36984202[source]▶
Right! I forgot about good ol’ Lipinski: https://en.wikipedia.org/wiki/Lipinski%27s_rule_of_five
replies(2): >>36984970 #>>36986934 #
mallomarmeasle ◴[03 Aug 23 12:32 UTC] No.36984970{3}[source]▶
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...

replies(2): >>36985009 #>>36991835 #
1. panabee ◴[03 Aug 23 21:01 UTC] No.36991835{4}[source]▶
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.