tyrosine kinase inhibitor

A tyrosine kinase inhibitor, usually shortened to TKI, is a drug that switches off a particular kind of cellular signaling enzyme. Tyrosine kinases act like relay stations that pass on growth and survival messages by tacking phosphate tags onto other proteins. In many cancers one of these relays is stuck in the on position, telling cells to keep growing; a TKI silences it.

Most TKIs are small molecules that slip into the kinase's ATP-binding pocket — the slot where the enzyme normally grabs the energy molecule it needs to add a phosphate. By occupying that slot, the drug blocks the chemical reaction the kinase carries out. Designing a good TKI is largely about fitting that pocket tightly while avoiding the hundreds of other kinases that share a similar pocket, so selectivity is a constant challenge.

TKIs transformed several cancers from fatal into manageable conditions, but tumors fight back. A mutation in the kinase that subtly reshapes the pocket can stop the drug from binding while leaving the enzyme active, driving relapse. This arms race has produced successive generations of TKIs, including covalent and allosteric designs meant to outflank resistance.