Hit Identification & Screening

biochemical assay

A biochemical assay tests a compound against the target protein itself, purified and placed in a tube — stripped of the cell and all its complexity. It is like testing a key on a lock you've taken off the door and laid on the workbench: you see exactly how the key fits the lock, without the surrounding house getting in the way.

Typically a purified target (an enzyme, receptor, or other protein) is combined with its substrate or ligand and the test compound in a defined buffer, and a clean readout reports the result — for an enzyme, the rate of product formation; for a binding interaction, displacement of a labeled ligand. Because the system contains only known components, the data are well-defined, easy to interpret quantitatively, and ideal for measuring exact potency values like IC50 and inhibition constants.

The price of that cleanliness is loss of context. A biochemical assay says nothing about whether the compound can cross a cell membrane, survive metabolism, or hit the target inside a living system, and a purified protein may adopt a conformation or lack partners present in the cell. That is why biochemical assays are usually paired with cell-based assays, which restore biological context at the cost of clarity.

A purified protease is mixed with a fluorogenic substrate; the test compound's IC50 is read directly from how much it slows the fluorescence increase.

With only purified components, a biochemical assay yields clean, quantitative potency.

Potency in a biochemical assay often differs from potency in cells: a compound can be a strong enzyme inhibitor in the tube yet weak in cells if it cannot get inside, or vice versa. The two readouts are complementary, not interchangeable.

Also called
in vitro biochemical assay体外生化检测法體外生化檢測法