For example, all approved SMKIs (e.g., pazopanib, sunitinib, and regorafenib) primarily targeting vascular endothelial growth factor receptor 2 (VEGFR2) share warnings of hypertension and bleeding5 (i.e., “on-target” side effect); however, these SMKIs also exhibit heterogenous kinase inhibition (KI) profiles beyond VEGFR2 inhibition, resulting in a broad range of toxicity and side effects in a variety of tissues and organs (i.e., “off-target” side effect). Here, KDR is linked to hypertensive disorder.