3 ms·

I’ve heard a theory that says the era of small molecules targeting single complexes is probably on the sharply downward slope of an asymptote. If we’re lucky th

I’ve heard a theory that says the era of small molecules targeting single complexes is probably on the sharply downward slope of an asymptote. If we’re lucky that will just mean new therapies which target complex systems rather than single-drug-targets is in sight. If we’re unlucky there will be a harsh gap between the two eras.

cassowary37 9y ago
Well, I think it's true that traditionally folks trying to do rational drug discovery are better at targeting certain proteins (cell surface receptors; some enzymes) with small molecules than others. Also true that first generation of most drugs were discovered serendipitously and only later was mechanism understood. BUT - notion that we're at the sharp downward slope would be a surprise to most pharmas and biotechs. While there's more of an emphasis on understanding entire pathways rather than single proteins, it's still generally the goal to find a single place in the pathway where a small molecule (or antibody, or whatever) will act. It's also /really/ hard to disrupt protein-protein interactions, though it's possible.
- cassowary37 9y ago
  And forgot to mention that there's all sorts of very cool new tools coming - one of my favorites is this one for targeted protein degradation: https://www.ncbi.nlm.nih.gov/pubmed/28223226 https://www.ncbi.nlm.nih.gov/pubmed/28223226
aaavl2821 9y ago
One could argue we are in the beginning of the harsh gap between the two eras. In 2012 the pharma industry contracted for the first time ever. Many industry insiders argue the traditional r&d model is broken There is an emerging wave of new therapeutic modalities (cell therapy, gene therapy, microbiome therapy, bioelecrronic medicine, etc) but it isn't clear if these will be as significant as antibodies were in the 1980s http://blogs.sciencemag.org/pipeline/archives/2017/11/28/a-grim-future-here-are-the-numbers http://blogs.sciencemag.org/pipeline/archives/2017/11/28/a-g...

cassowary37 9y ago

Well, I think it's true that traditionally folks trying to do rational drug discovery are better at targeting certain proteins (cell surface receptors; some enzymes) with small molecules than others. Also true that first generation of most drugs were discovered serendipitously and only later was mechanism understood. BUT - notion that we're at the sharp downward slope would be a surprise to most pharmas and biotechs. While there's more of an emphasis on understanding entire pathways rather than single proteins, it's still generally the goal to find a single place in the pathway where a small molecule (or antibody, or whatever) will act. It's also /really/ hard to disrupt protein-protein interactions, though it's possible.

cassowary37 9y ago
And forgot to mention that there's all sorts of very cool new tools coming - one of my favorites is this one for targeted protein degradation: https://www.ncbi.nlm.nih.gov/pubmed/28223226 https://www.ncbi.nlm.nih.gov/pubmed/28223226

aaavl2821 9y ago

One could argue we are in the beginning of the harsh gap between the two eras. In 2012 the pharma industry contracted for the first time ever. Many industry insiders argue the traditional r&d model is broken There is an emerging wave of new therapeutic modalities (cell therapy, gene therapy, microbiome therapy, bioelecrronic medicine, etc) but it isn't clear if these will be as significant as antibodies were in the 1980s http://blogs.sciencemag.org/pipeline/archives/2017/11/28/a-grim-future-here-are-the-numbers http://blogs.sciencemag.org/pipeline/archives/2017/11/28/a-g...