Lipoxygenase (LO) is a biological target for many diseases such as asthma, atherosclerosis, and cancer. Our labs have synthesized and investigated nordihydroguaiaretic acid (NDGA) derivatives and have established that the reductive inhibition of soybean and 15-human LO can be affected by the strength of the electron-withdrawing substituents on the phenyl rings of NDGA. In addition, we have determined that hydrophobic NDGA derivatives activate 15-HLO, suggesting a hydrophobic allosteric site.