Few tamoxifen users have suffered from increased rates of uterine cancer, hot flushes, and thromboembolisms. The drug can also cause hepatocarcinomas in rats. This is likely due to the ethyl group of the tamoxifen stilbene core that is subject to allylic oxidative activation causing DNA alkylation and strand scission. This problem is later corrected in toremifene. Tamoxifen is more promiscuous than raloxifene in target sites because of the relationship between ER's amino acid in Asp-351 and the antiestrogenic side chain of the SERM. The side chain for tamoxifen cannot neutralize Asp-351, so the site allosterically influences AF-1 at the proximal end of the ER. This issue is mended with the second-generation drug raloxifene.