See what you think about this PDF: Cyclofluidics is advertising the “Robot Medicinal Chemist”. It’s an integrated microfluidics synthesis platform, assay/screening module, with software to decide what the next round of analogs should be:
Potential lead molecules are synthesised, purified and screened in fast serial mode, incorporating activity data from each compound as it is generated before selecting the next compound to make.
To ensure data quality, each compound is purified by integrated high pressure liquid chromatography (HPLC), its identity confirmed by mass spectrometry and the
concentration entering the assay determined in real time by evaporative light scattering detection (ELSD). The compound’s IC50 is then measured in an on-line biochemical assay and this result fed into the design software before the algorithm selects the next compound to make – thus generating structure-activity relationship data. The system is designed to use interchangeable design algorithms, assay formats and chemistries and at any stage a medicinal chemist can intervene in order to adjust the design strategy.
I can see where this might work, but only in special cases. The chemistry part would seem to require a “core with substituents” approach, where a common intermediate gets various things hung off of it. (That’s how a lot of medicinal chemistry gets done anyway). Flow chemistry has improved to where many reactions would be possible, but each new reaction type would have to be optimized a bit before you turned the machine loose, I’d think.
The assay part is more problematic. There are assays suitable for in-line evaluation like this, but there are plenty of others that aren’t. (I would think that SPR would be particularly well-suited, since it operates in flow, anyway). But that prior optimization that the chemistry needs is needed even more here, to make sure that things are robust enough that the machine doesn’t generate crappy numbers (and more swiftly than you could do by hand!)
The software is the part I’m really wondering about. How is this thing picking the next round of analogs? Physiochemical descriptions like logD? Some sort of expert system with med-chem lore in it? Does it do any modeling or conformational analysis? Inquiring minds want to know. And I’d also like to know if they’ve sold any of these systems so far, and to hear some comments from their users.
Update: here’s one.