Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization.

Background: Overexpression or mutation of the epidermal growth factor receptor (EGFR) potently enhances the growth of many solid tumors. Tumor cells frequently display resistance to mechanistically-distinct EGFR-directed therapeutic agents, making it valuable to develop therapeutics that work by additional mechanisms. Current EGFR-targeting therapeutics include antibodies targeting the extracellular domains, and small molecules inhibiting the intracellular kinase domain.

Sunitinib, a receptor tyrosine kinase inhibitor, increases blood pressure in rats without associated changes in cardiac structure and function.

Background: Sunitinib, a multi-tyrosine kinase inhibitor has demonstrated clinical activity in advanced renal cell carcinoma and imatinib-resistant/intolerant gastrointestinal stromal tumor. It has been associated with manageable hypertension and other unique toxicities.

Aims: Two nonclinical studies were conducted to determine if sunitinib has direct/indirect effects on cardiac structure/function that may be related to hypertension at clinically relevant exposures.