Engineering
Chemical Space.
The universe of drug-like molecules is estimated at 1060. We have explored less than 0.0000001% of it.We are not finding drugs; we are designing molecular machines.
The Math Problem
There are more potential small molecules than atoms in the solar system. Traditional High-Throughput Screening (HTS) tests ~106 compounds. That is searching a beach by picking up one grain of sand.
To solve longevity, we need to access DNA-Encoded Libraries (DELs) allowing us to screen billions of compounds in a single test tube using PCR barcodes.
Beyond Inhibition
"Blocking" a protein is archaic. We are entering the era of proximity-induced pharmacology. We turn the cell's own machinery against the disease.
PROTACs
Bifunctional molecules that hijack the Ubiquitin-Proteasome System. One end binds the target, the other binds an E3 Ligase. Result: The target is marked for destruction.
Molecular Glues
Small molecules that reshape the surface of a protein to create a novel binding interface (neo-substrate). Nature's way of rewiring protein-protein interactions.
Allosteric Modulation
Binding to a distal site to induce a conformational change. This offers exquisite selectivity, targeting specific protein states rather than just the active site.