Similar to the PI3K/AKT/mTOR pathway, the MAPK/Erk signaling cascade is activated by a wide variety of receptors involved in growth and differentiation including receptor tyrosine kinases (RTKs), integrins, ion channels, and extracellular stimuli such as heat and stress. The specific components of the cascade vary greatly among different stimuli, but the architecture of the pathway usually includes a set of adaptors (e.g. Shc, GRB2, Crk, etc.) linking the receptor to a guanine nucleotide exchange factor (SOS, C3G, etc.) transducing the signal to small GTP binding proteins (Ras, Rap1), which in turn activate the core unit of the cascade composed of a MAPKKK (Raf), a MAPKK (MEK1/2), and MAPK (Erk: extracellular signal-regulated kinases). An activated Erk dimer can regulate targets in the cytosol and also translocate to the nucleus where it phosphorylates a variety of transcription factors regulating gene expression[1],[2]. One example of the most recent additions to this class of compounds is FMK (Axon 1848), a potent, highly specific and irreversible inhibitor of p90 ribosomal protein S6 kinase RSK1 and RSK2. This drug is capable of inducing significant apoptosis in human FGFR3-expressing, t(4;14)-positive multiple myeloma cells[3]. Actually, MEK enzymes are members of the class of dual specificity mitogen-activated protein kinase kinase (EC 2.7.12.2) and should not be listed within the section of serine/threonine specific kinases (EC 2.7.11.). However, as they are integral members of the group of enzymes involved in MAPK/ERK signaling, and besides having the capability to phosphorylate tyrosine residues, they are also capable of phosphorylating serine/threonine sites of substrates, MEK inhibitors are listed in this section for kinases involved in the MAPK/ERK signaling pathway.