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SMALL-MOLECULE PROBES Colchicine, a probe of tubulin³; spidamine, used to study glutamate receptor function⁵; reserpine, used to discover the neurotransmitter dopamine⁶; phorbol (parent alcohol of a family of diesters), used to study a family of protein kinases⁷; pioglitazone (Actos), an activator of the transcription factor PPARg⁸; MK-886, used to discover the protein 5-lipoxygenase-activating protein (FLAP)⁹; somatostatin receptor agonist, used to study a specific receptor's physiological functions¹⁰; 506BD, a probe of immunophilin action^11,12; dimerizer (methallylrapamycin), an inactive ("bumped") variant of rapamycin that, by chemical modification, gained the ability to control proximal relations of signaling proteins in cells and animals¹⁷; rapamycin, a probe of the nutrient-response signaling network and of the proteins FRAP and TOR²⁰; K-trap affinity reagent (lysine variant of trapoxin), used to discover HDAC1.²³

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