antimetabolite

An antimetabolite is a drug that disguises itself as one of the cell's normal building blocks. To make DNA and RNA, a cell needs nucleotides and the small molecules used to assemble them. An antimetabolite looks enough like one of these that the cell's enzymes pick it up — but once inside the machinery it gums up the works, like a counterfeit coin that jams a vending machine.

Some antimetabolites are false versions of nucleotide bases or sugars that get incorporated into DNA or RNA and stall replication. Others mimic vitamins or co-factors and shut down the enzymes that synthesize nucleotides from scratch. Because a dividing cell needs a fresh full set of DNA building blocks, cells that are racing to divide — including cancer cells — are the most vulnerable.

Antimetabolites were among the first rationally targeted cancer drugs and are still heavily used. Their downside is the familiar one of broad chemotherapy: healthy fast-dividing tissues suffer too, and tumors can develop resistance by changing the enzymes that activate the drug or that the drug is meant to block.