is it surprising that nucleotide analogs are good cancer drugs, but not (to my knowledge) ribosomal poisons or anti-protein synthesis drugs?

There are nucleotide RNA analogs aimed against RNA viruses (e.g. molnupiravir).
I think the genomic molecule (be it DNA or RNA) is less tolerant to modified nucleotides compared to the mRNA and any ncRNA

@Caroline_Bartma it’s a good question but it doesn’t surprise me. It’s what I’d expect from first principles. Nucleotide analogs will be specifically toxic to actively proliferating cells because they’re doing DNA synthesis and dividing. Ribosomal poisons like cyclohexamide zap everything, fast growing or not - I’d expect the toxicity to be too high to be therapeutically useful.

@Caroline_Bartma I think these are good targets for plasma cell derived tumors - especially if you factor in the entire cycle of protein homeostasis, with proteasome inhibitors being a big deal in the clinic. But the basic issue is what do you expect the side effect profile to be? Targeting nucleic acid synthesis is broad, but still the list of fast dividing host tissues/cells at any given timepoint might be significantly larger than those doing medium to high level protein synthesis. With plasma cells being just one big outlier.

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