KT-5720 is prepared by a modificiation of K-252a (sc-200517), which is synthesized by the fungus Nocardiopsis sp. KT-5720 is a potent, specific and cell-permeable inhibitor of PKA (Ki = 60 nM). This compound blocks PKA signaling through competitive inhibition. KT 5720 does not affect the activity of other kinases, including pKC, pKG, or MLCK and can inhibit axon branching in cultured neurons. KT-5720 has been shown to reversibly arrest human skin fibroblasts in the G1 phase of the cell cycle and regulate multiple signal transduction events vis-a-vis protein phosphorylation and cellular responses involving the cyclic AMP messenger system. This compound reversed suppression of mistletoe lectin II (MLII) by dibutyl-cAMP in HL-60 cells. KT-5720 shows inhibitor effects on PHK, PDK1, MEK, MSK1, Akt1 (PKBα) and GSK3β. KT-5720 has numerous actions unrelated to its ability to inhibit PKA. This suggests that other PKA inhibitors should be used in its place. Although KT 5720 has been extremely useful in examining the roles of PKA in cell signaling, it may now be time for them to be superseded by other methods.