The presentation will focus on the generation of highly effective signaling inhibitors targeting members of the erbB family of receptor tyrosine kinases,  EGFR and ErbB-2, also known as transmembrane Type 1 receptor tyrosine kinases of the HER family of receptors. Type 1 receptors are over-expressed in a variety of cancers and generally correlate with poor prognosis. For this reason, we targeted the ATP binding site of the intracellular portion of the protein to block the aberrant signaling event which led to the discovery of Tykerb (lapatinib, GW572016).